Intragastric device

ABSTRACT

Devices and methods for treating obesity are provided. More particularly, intragastric devices and methods of fabricating, deploying, inflating, monitoring, and retrieving the same are provided.

INCORPORATION BY REFERENCE TO RELATED APPLICATIONS

Any and all priority claims identified in the Application Data Sheet, orany correction thereto, are hereby incorporated by reference under 37CFR 1.57. This application is a continuation of U.S. application Ser.No. 15/690,095, filed Aug. 29, 2017, which is a continuation of U.S.application Ser. No. 14/860,538, filed Sep. 21, 2015, now U.S. Pat. No.9,827,128, which is a continuation of U.S. application Ser. No.14/227,195, filed Mar. 27, 2014, now U.S. Pat. No. 9,351,862, which is acontinuation of U.S. application Ser. No. 13/510,921, filed on May 18,2012, now U.S. Pat. No. 8,740,927, which is the national phase under 35U.S.C. § 371 of prior PCT International Application No.PCT/US2011/022165 which has an International Filing Date of Jan. 21,2011. Each of the aforementioned applications is incorporated byreference herein in its entirety, and each is hereby expressly made apart of this specification.

FIELD OF THE INVENTION

Devices and methods for treating obesity are provided. Moreparticularly, intragastric devices and methods of fabricating,deploying, inflating, monitoring, and retrieving the same are provided.

BACKGROUND OF THE INVENTION

Obesity is a major health problem in developed countries. Obesity putsyou at greater risk of developing high blood pressure, diabetes and manyother serious health problems. In the United States, the complicationsof being overweight or obese are estimated to affect nearly one in threeAmerican adults, with an annual medical cost of over $80 billion and,including indirect costs such as lost wages, a total annual economiccost of over $120 billion. Except for rare pathological conditions,weight gain is directly correlated to overeating.

Noninvasive methods for reducing weight include increasing metabolicactivity to burn calories and/or reducing caloric intake, either bymodifying behavior or with pharmacological intervention to reduce thedesire to eat. Other methods include surgery to reduce the stomach'svolume, banding to limit the size of the stoma, and intragastric devicesthat reduce the desire to eat by occupying space in the stomach.

Intragastric volume-occupying devices provide the patient a feeling ofsatiety after having eaten only small amounts of food. Thus, the caloricintake is diminished while the person is satisfied with a feeling offullness. Currently available volume-occupying devices have manyshortcomings. For example, complex gastric procedures are required toinsert some devices.

U.S. Pat. No. 4,133,315, the contents of which are incorporated hereinby reference in their entirety, discloses an apparatus for reducingobesity comprising an inflatable, elastomeric bag and tube combination.The bag can be inserted into the patient's stomach by swallowing. Theend of the attached tube distal to the bag remains in the patient'smouth. A second tube is snaked through the nasal cavity and into thepatient's mouth. The tube ends located in the patient's mouth areconnected to form a continuous tube for fluid communication through thepatient's nose to the bag. Alternatively, the bag can be implanted by agastric procedure. The bag is inflated through the tube to a desireddegree before the patient eats so that the desire for food is reduced.After the patient has eaten, the bag is deflated. The tube extends outof the patient's nose or abdominal cavity throughout the course oftreatment.

U.S. Pat. Nos. 5,259,399, 5,234,454 and 6,454,785, the contents of whichare incorporated herein by reference in their entirety, discloseintragastric volume-occupying devices for weight control that must beimplanted surgically.

U.S. Pat. Nos. 4,416,267, 4,485,805, 4,607,618, 4,694,827, 4,723,547,4,739,758, and 4,899,747 and European Patent No. 246,999, the contentsof which are incorporated herein by reference in their entirety, relateto intragastric, volume-occupying devices for weight control that can beinserted endoscopically. Of these, U.S. Pat. Nos. 4,416,267, 4,694,827,4,739,758 and 4,899,747, the contents of which are incorporated hereinby reference in their entirety relate to balloons whose surface iscontoured in a certain way to achieve a desired end. In U.S. Pat. Nos.4,416,267 and 4,694,827, the contents of which are incorporated hereinby reference in their entirety, the balloon is torus-shaped with aflared central opening to facilitate passage of solids and liquidsthrough the stomach cavity. The balloon of U.S. Pat. No. 4,694,827, thecontents of which are incorporated herein by reference in theirentirety, has a plurality of smooth-surfaced convex protrusions. Theprotrusions reduce the amount of surface area which contacts the stomachwall, thereby reducing the deleterious effects resulting from excessivecontact with the gastric mucosa. The protrusions also define channelsbetween the balloon and stomach wall through which solids and liquidsmay pass. The balloon of U.S. Pat. No. 4,739,758, the contents of whichare incorporated herein by reference in their entirety, has blisters onits periphery that prevent it from seating tightly against the cardia orpylorus.

The balloons of U.S. Pat. Nos. 4,899,747 and 4,694,827, the contents ofwhich are incorporated herein by reference in their entirety, areinserted by pushing the deflated balloon and releasably attached tubingdown a gastric tube. U.S. Pat. No. 4,723,547, the contents of which areincorporated herein by reference in their entirety discloses a speciallyadapted insertion catheter for positioning its balloon. In U.S. Pat. No.4,739,758, the contents of which are incorporated herein by reference intheir entirety, the filler tube effects insertion of the balloon. InU.S. Pat. No. 4,485,805, the contents of which are incorporated hereinby reference in their entirety, the balloon is inserted into a fingercot that is attached by string to the end of a conventional gastric tubethat is inserted down the patient's throat. The balloon of EuropeanPatent No. 246,999 is inserted using a gastroscope with integralforceps.

In U.S. Pat. Nos. 4,416,267, 4,485,805, 4,694,827, 4,739,758, and4,899,747 and European Patent No. 246,999, the contents of which areincorporated herein by reference in their entirety, the balloon isinflated with a fluid from a tube extending down from the patient'smouth. In these patents, the balloon also is provided with aself-sealing hole (U.S. Pat. No. 4,694,827, the contents of which areincorporated herein by reference in their entirety), injection site(U.S. Pat. Nos. 4,416,267 and 4,899,747, the contents of which areincorporated herein by reference in their entirety), self-sealing fillvalve (U.S. Pat. No. 4,485,805, the contents of which are incorporatedherein by reference in their entirety), self-closing valve (EuropeanPatent No. 246,999, the contents of which are incorporated herein byreference in their entirety) or duck-billed valve (U.S. Pat. No.4,739,758, the contents of which are incorporated herein by reference intheir entirety). U.S. Pat. No. 4,723,547, the contents of which areincorporated herein by reference in their entirety, uses an elongatedthick plug and the balloon is filled by inserting a needle attached toan air source through the plug.

U.S. Pat. No. 4,607,618, the contents of which are incorporated hereinby reference in their entirety, describes a collapsible appliance formedof semi-rigid skeleton members joined to form a collapsible hollowstructure. The appliance is not inflatable. It is endoscopicallyinserted into the stomach using an especially adapted bougie having anejector rod to release the collapsed appliance. Once released, theappliance returns to its greater relaxed size and shape.

U.S. Pat. No. 5,129,915, the contents of which are incorporated hereinby reference in their entirety, the contents of which are incorporatedherein by reference, relates to an intragastric balloon that is intendedto be swallowed and that inflates automatically under the effect oftemperature. Three ways that an intragastric balloon might be inflatedby a change in temperature are discussed. A composition comprising asolid acid and non-toxic carbonate or bicarbonate is separated fromwater by a coating of chocolate, cocoa paste or cocoa butter that meltsat body temperature. Alternatively, citric acid and an alkalinebicarbonate coated with non-toxic vegetable or animal fat melting atbody temperature and which placed in the presence of water, can producethe same result. Lastly, the solid acid and non-toxic carbonate orbicarbonate are isolated from water by an isolation pouch oflow-strength synthetic material which it will suffice to breakimmediately before swallowing the bladder. Breaking the isolationpouches causes the acid, carbonate or bicarbonate and water to mix andthe balloon to begin to expand immediately. A drawback of thermaltriggering of inflation is that it does not afford the degree of controland reproducibility of the timing of inflation that is desirable andnecessary in a safe self-inflating intragastric balloon.

SUMMARY OF THE INVENTION

A free-floating, intragastric, volume-occupying device that can beinserted into the stomach by the patient swallowing it and lettingperistalsis deliver it into the stomach in the same manner that food isdelivered, or by positioning it with a catheter, is desirable.

Volume-occupying devices and methods for manufacturing, deploying,inflating, tracking, deflating and retrieving of such devices areprovided. The devices and methods of the preferred embodiments may beemployed for treating over weight and obese individuals. Methodsemploying the device of the preferred embodiments may be swallowed by apatient, with or without a catheter attached. Once in the stomach of thepatient, the device is inflated with a preselected gas or mixture ofgases, to a preselected volume. After a predetermined time period, thedevice can be removed using endoscopic tools or decreases in volume ordeflate so as to pass through the remainder of the patient's digestivetract.

Inflation may be achieved by use of a removable catheter that initiallyremains in fluid contact with the device after it has been swallowed bythe patient.

The volume-occupying subcomponent of devices may be formed by injection,blow or rotational molding of a flexible, gas-impermeable, biocompatiblematerial, such as, for example, polyurethane, nylon or polyethyleneterephthalate. Materials that may be used to control the gaspermeability/impermeability of the volume-occupying subcomponentinclude, but are not limited to, silicon oxide (SiOx), gold or any noblemetal, saran, conformal coatings and the like, when it is desired toreduce permeability. To enhance gas-impermeable characteristics of thewall of the device, if desirable, the volume-occupying subcomponent maybe further coated with one or more gas-barrier compounds, or be formedof a Mylar polyester film coating or kelvalite, silver or aluminum as ametallicized surface to provide a gas impermeable barrier.

In further embodiments, the device employs a delivery state in which thedevice is packaged such that the device may be swallowed while producingminimal discomfort to the patient. In a delivery state, the device maybe packaged into a capsule. Alternatively, the device may be coated witha material operable to confine the device and facilitate swallowing.Various techniques may also be employed to ease swallowing of the deviceincluding, for example, wetting, temperature treating, lubricating, andtreating with pharmaceuticals such as anesthetics.

In other embodiments, the devices may incorporate a tracking orvisualization component that enables physicians to determine thelocation and/or orientation of the device within the patient's body.Tracking subcomponents may include incorporating a barium stripe orgeometric shape into the wall of the volume-occupying subcomponent.Tracking and visualization, may also be achieved by incorporation of amicrochip, infrared LED tag, ultraviolet absorbing compounds,fluorescent or colored compounds and incorporation of metallized stripsand patterns into the volume-occupying subcomponent or othersubcomponents of the device. Such techniques may also be used to obtaincertain device specific information and specifications while the deviceremains inside the patient's body.

In a first aspect, a system is provided for inflating an intragastricballoon, the system comprising: an inflation catheter, wherein theinflation catheter comprises a needle assembly comprising a hollowneedle, a bell-shaped needle sleeve, and a mechanism for detachment ofthe inflation catheter after inflation of a balloon in vivo is complete;an intragastric balloon comprising a polymeric wall, wherein thepolymeric wall comprises one or more layers, and a balloon valve systemcomprising a self-sealing septum in a retaining structure, wherein theseptum is configured for piercing by the needle, wherein the retainingstructure comprises a concentric valve system with a smaller innercylinder housing the septum and a larger outer cylinder housing amaterial providing compressive forces against the bell-shaped needlesleeve of the inflation catheter for inflation and detachment, whereinthe material providing compressive forces is a harder durometer materialthan the septum, and wherein the smaller inner cylinder comprises a lipconfigured for an interference fit with the bell-shaped needle sleeve toprovide sealing of the valve to the inflation catheter sufficient tomaintain the seal during inflation of the balloon; a balloon outercontainer; and an inflation source container, wherein the inflationsource container is configured to connect to the inflation catheter;wherein the inflation catheter connected to the intragastric balloonprior to inflation is of a size and shape configured for swallowing by apatient in need thereof.

In an embodiment of the first aspect, the polymeric wall comprises abarrier material comprising of nylon/polyethylene.

In an embodiment of the first aspect, the polymeric wall comprises abarrier material comprising of nylon/polyvinylidenechloride/polyethylene.

In an embodiment of the first aspect, the outer container is selectedfrom the group consisting of a push-fit capsule, a wrap, and a band, andwherein the outer container comprises a material selected from the groupconsisting of gelatin, cellulose, and collagen.

In an embodiment of the first aspect, the septum is cone-shaped.

In an embodiment of the first aspect, the inflation source container isconfigured to connect to the inflation catheter via a connector or aninflation valve.

In an embodiment of the first aspect, the inflation catheter is from 1French to 6 French in diameter, and is from about 50 cm to about 60 cmin length.

In an embodiment of the first aspect, the inflation catheter is a duallumen catheter comprising an inflation lumen and a detachment lumen,wherein the inflation lumen is in fluid connection to the inflationsource container, and wherein the detachment lumen is configured forconnection to a detachment liquid source container, wherein thedetachment liquid comprises a physiological compatible liquid, andwherein the interference fit is insufficient to maintain a seal uponapplication of a hydraulic pressure by the detachment liquid, such thatupon application of the hydraulic pressure to the needle assembly it isejected from the balloon valve.

In an embodiment of the first aspect, the inflation catheter comprises asingle lumen and a structural member providing increased tensilestrength, and an inflation valve configured for connecting the singlelumen to the inflation source container and a detachment liquid sourcecontainer, wherein the detachment liquid comprises a physiologicalcompatible liquid, and wherein the interference fit is insufficient tomaintain a seal upon application of a hydraulic pressure by thedetachment liquid, such that upon application of the hydraulic pressureto the needle assembly it is ejected from the balloon valve.

In an embodiment of the first aspect, the inner cylinder is configuredto control alignment of the needle assembly with the septum, provide abarrier to the needle piercing the polymeric wall, and providecompression such that the septum reseals after inflation and needlewithdrawal.

In an embodiment of the first aspect, a plurality of intragastricballoons is connected to a single inflation catheter.

In an embodiment of the first aspect, the inflation catheter is of avariable stiffness.

In an embodiment of the first aspect, the inflation source comprises asyringe.

In an embodiment of the first aspect, the inflation source is configuredto utilize information regarding inflation pressure as a function oftime to provide feedback to a user, wherein the feedback indicates acondition selected from the group consisting of failure by mechanicalblockage, failure by esophagus constraint, failure by inflation catheterleak or detachment, and successful balloon inflation.

In a second aspect, a method is provided for inflating an intragastricballoon, the method comprising: providing an intragastric balloon in anouter container, the intragastric balloon comprising a polymeric wall,wherein the polymeric wall comprises one or more layers, and a balloonvalve system comprising a self-sealing septum in a retaining structure,wherein the retaining structure comprises a concentric valve system witha smaller inner cylinder housing the septum and a larger outer cylinderhousing a material configured to provide compressive forces against abell-shaped needle sleeve of an inflation catheter, wherein the materialproviding compressive forces is a higher durometer material than theseptum, and wherein the smaller inner cylinder comprises a lipconfigured for an interference fit with the bell-shaped needle sleeve;providing an inflation catheter comprising a needle assembly, the needleassembly comprising a hollow needle, a bell-shaped needle sleeve;piercing the septum by the needle of an inflation catheter, whereby aninterference fit is created between the bell-shaped needle sleeve andthe lip of the smaller inner cylinder; causing the intragastric balloonin an outer container attached by the interference fit to the inflationcatheter to be swallowed by a patient in need thereof; degrading theouter container so as to permit inflation of the intragastric balloon;inflating the intragastric balloon in the patient's stomach via theinflation catheter, wherein the inflation catheter is connected to aninflation fluid source container; and detaching the intragastric balloonfrom the inflation catheter, wherein a detachment liquid comprising aphysiological compatible liquid is forced through the inflation catheterto apply hydraulic pressure to the needle assembly such that theinterference fit between the lip and the bell-shaped needle sleeve isbroken, the needle assembly is ejected from the balloon valve and theself-sealing septum reseals.

In an embodiment of the second aspect, the inflation catheter is a duallumen catheter comprising an inflation lumen and a detachment lumen,wherein the inflation lumen is configured for fluid connection to theinflation source container, and wherein the detachment lumen isconfigured for connection to a detachment liquid source container fordetachment of the balloon.

In an embodiment of the second aspect, the inflation catheter is asingle lumen catheter comprising a structural member providing increasedtensile strength and an inflation valve configured for first connectingthe single lumen catheter to the inflation source container and then toa detachment liquid source container for detachment of the balloon.

In an embodiment of the second aspect, wherein the method furthercomprises monitoring inflation pressure as a function of time anddetaching when a predetermined ending pressure is obtained, whereinsuccessful balloon inflation is indicated by achievement of thepreselected ending pressure, which is based on a starting pressure inthe inflation source and an inflation volume of the balloon.

In a third aspect, a method is provided for deflating an intragastricballoon, the method comprising: providing an intragastric balloon in anin vivo intragastric environment, the intragastric balloon comprising apolymeric wall and a valve system, the valve system comprising aself-sealing valve, a casing, an outer sealing member, a rigid retainingstructure, and a deflation component; wherein the casing has one or morevent pathways and a lip configured to hold the outer sealing member inplace, wherein the outer sealing member is positioned to block the oneor more vent pathways when in place, wherein the rigid retainingstructure provides support to the septum and the outer sealing member,and wherein the deflation component is situated in the casing and behindthe retaining structure; exposing the deflation component to moistureinside of the balloon via the one or more vent pathways, whereby thedeflation component expands, pushing the retaining structure and thusthe outer sealing member linearly past the lip of the casing to open theone or more vent pathways so as to provide fluid communication betweenthe in vivo gastric environment and a lumen of the balloon; anddeflating the balloon through the one or more vent pathways.

In an embodiment of the third aspect, the deflation component comprisesa solute material encapsulated in a binder material, wherein thedeflation component is further surrounded by moisture limiting materialthat has a predefined moisture vapor transmission rate.

In an embodiment of the third aspect, the solute material is apolyacrylamide.

In an embodiment of the third aspect, the rigid retaining structure andthe casing has a press fit lock that prevents the rigid retainingstructure from being expelled from the casing after maximum displacementby the deflation component.

In a fourth aspect, a method is provided for deflating an intragastricballoon, the method comprising: providing an intragastric balloon in anin vivo intragastric environment, the intragastric balloon comprising apolymeric wall, a self-sealing valve system, and a deflation system, thedeflation system comprising a casing, a sealing member, a plunger, and adeflation component; wherein the casing has one or more vent pathwaysand is secured in the polymeric wall, wherein the plunger providessupport to the sealing member and maintains the sealing member inposition to block the one or more vent pathways in the casing when inplace, and wherein the deflation component is situated in the casing andbehind the plunger; exposing the deflation component to moisture insideof the balloon via the one or more vent pathways, whereby the deflationcomponent expands, pushing the plunger and thus the sealing memberlinearly through the casing to open the one or more vent pathways so asto provide fluid communication between the in vivo gastric environmentand a lumen of the balloon; and deflating the balloon through the one ormore vent pathways.

In an embodiment of the fourth aspect, the intragastric balloon furthercomprises a water retaining material situated between the deflationcomponent and the one or more vent pathways, wherein the water retainingmaterial is configured to retain water and to hold it against a surfaceof the deflation component in order to maintain a constant moistureenvironment.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-D depict a perspective view (FIG. 1A), a side view (FIG. 1B), atop view (FIG. 1C) and a cross-sectional view (FIG. 1D) of a headassembly of a self-sealing valve system which contains a self-sealingseptum housed within a metallic concentric cylinder.

FIGS. 2A-D depict a perspective view (FIG. 2A), a side view (FIG. 2B), across-sectional view (FIG. 2C), and a top view (FIG. 2C) of tube systemwith rings. It includes a smaller cylinder of a concentric metallicretaining structure into which a septum can be inserted or otherwisefabricated into, as in the self sealing valve system of FIGS. 1A-D.

FIGS. 3A-C depict a perspective view (FIG. 3A), a side view (FIG. 3B),and a top view (FIG. 3C) of a ring stop—an additional ring placed at thedistal end of an inner cylinder to provide additional compression toensure the septum material is dense enough to re-seal itself, as in theself sealing valve system of FIGS. 1A-D.

FIGS. 4A-D depict a perspective view (FIG. 4A), a side view (FIG. 4B), across-sectional view (FIG. 4C) and a top view (FIG. 4D) of a head unitcomprising an outer cylinder of a concentric valve housing comprising ahigher durometer material than the inner cylinder, as in the selfsealing valve system of FIGS. 1A-D.

FIGS. 5A-C depict a perspective view (FIG. 5A), a side view (FIG. 5B),and a top view (FIG. 5C) a ring retainer—an additional retaining ring tofurther enhance the seal between the metal and the valve silicone, as inthe self sealing valve system of FIGS. 1A-D.

FIG. 6 depicts a connector for a dual lumen catheter.

FIG. 7 depicts an inflation valve.

FIGS. 8A-B depicts a universal balloon valve for connection to aninflation catheter and a balloon encased in an outer container. FIG. 8Adepicts the valve coupled to the inflation catheter, and FIG. 8B depictsthe valve further coupled to the encased balloon.

FIGS. 9A-C depict a side view (FIG. 9B), a bottom view (FIG. 9B) and atop view (FIG. 9C) of a dual lumen catheter coupled to a gel capencapsulating a balloon.

FIGS. 10A-D depict a perspective view (FIG. 10A), a side view (FIG.10B), a top view (FIG. 10C), and a cross-sectional view (FIG. 10C) of abell-shaped needle sleeve.

FIGS. 11A-C depict various embodiments of a single lumen catheter. FIG.11A depicts the single lumen catheter with bell-shaped needle sleeveprotecting the needle. FIG. 11B shows a perspective cross-sectional viewof the single lumen catheter showing detail of the needle, bell-shapedneedle sleeve, and tensile cord. FIG. 11C shows a perspectivecross-sectional view of the single lumen catheter showing additionaldetail of the needle and bell-shaped needle sleeve when seated in thehead including the self-sealing valve system of FIGS. 1A-D.

FIGS. 12A-D depict a perspective view (FIG. 12A), a side view (FIG.12B), a top view (FIG. 12C), and a cross-sectional view (FIG. 12C) of aneedle sleeve configured to accommodate a larger diameter tube.

FIG. 13 depicts a variable stiffness catheter for administering agastric balloon.

FIGS. 14A-C depict an inflation fluid container system (FIG. 14A)including a connector (FIG. 14B) to the catheter and a pressure gauge(FIG. 14C).

FIG. 15 depicts a stainless steel inflation fluid container.

FIG. 16 is a graph depicting pressure as a function of time (pressuredecay), obtained from feedback from an inflation source container.

FIG. 17 depicts the expected decay curve for pressure sources using aspring mechanism or a balloon-within-balloon mechanism.

FIGS. 18A-B depict a top view (FIG. 18A) and side view (FIG. 18B) of aballoon showing the configuration of balloon seams for fabricating aballoon which resists bursting in vivo.

FIGS. 19A-D depict various embodiments of an eroding core to achievedeflation of a balloon. FIG. 19A (perspective view) and FIG. 19B (sideview) depict an eroding core with a protective barrier between the coreand the intragastric environment. In another embodiment, a seal is heldin place against the housing by an eroding core (FIG. 19C). After thecore erodes (FIG. 19D), the seal is released from against the housing.

FIG. 20 depicts a one-piece seal with protective canopy.

FIG. 21A depicts a deflation mechanism utilizing an erodible core in aradial ring seal, with compression ring to expel the seal once supportfrom the erodible core is removed. FIG. 21B depicts a deflationmechanism utilizing a seal with eroding core and a push out spring. FIG.21C depicts a moisture expanding material that pulls the septum out ofposition to cause balloon deflation.

FIGS. 22A-B depicts a plug in the wall of the balloon that contains acompressed pellet or gas releasing pellet. FIG. 22A depicts a compressedview and FIG. 22B depicts an expanded view of the gas pellet.

FIG. 23 depicts a top view of an outermost layer of a balloon “scored”or hatched with erodible material to create small channels that erodeover time.

FIGS. 24A-E depicts a composite wall of a balloon including severalmaterial layers (FIG. 24A and FIG. 24B, showing detail of FIG. 24A) thatare slowly penetrated by water that has been injected inside the balloonduring the manufacturing process or during the inflation process,causing rupture of a thin external protective later (FIG. 24C). Thewater can penetrate through a hole (FIG. 24D) and the balloon caninclude a weakened area of a patch bond to control the rupture location(FIG. 24E).

FIGS. 25A-B depict a top view (FIG. 25A) and a cross section (FIG. 25B)of a pressure sealing button that is adhesively bonded over aperforation in the balloon material for deflation.

FIGS. 26A-B depicts a top view (FIG. 26A), perspective view (FIG. 26B)and perspective view with inner detail (FIG. 26C) of connecting portswithin a septum attached to the balloon composite wall, wherein theports contain a water-dissolving or acid-dissolving material. Aplurality of ports and channels can be provided in a configurationutilizing an expanding material and push-out component as depicted inthe system of FIG. 26D (perspective view with inner detail) and FIG. 26E(cross-section).

FIGS. 27A-D depicts a port that encompasses an inflation and deflationmechanism in the same location. FIG. 27A depicts a cross-section of themechanism with the seal blocking the vents. FIG. 27B depicts a crosssection of the mechanism with the seal displaced, enabling fluidcommunication through the vent. An iso image of the mechanism with theseal displaced, enabling fluid communication through the vent isprovided in FIG. 27C. An iso image of the mechanism positioned forinflation of the balloon is provided in FIG. 27D.

FIGS. 28A-D depicts a deflation port. FIG. 28A depicts a cross-sectionof the deflation mechanism with the seal blocking the vents. FIG. 28Bdepicts a cross section of the deflation mechanism with the sealdisplaced, enabling fluid communication through the vent. An iso imageof the mechanism with the seal blocking the vents is provided in FIG.28C. An iso image of the mechanism with the seal displaced, enablingfluid communication through the vent, is provided in FIG. 28D.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The following description and examples illustrate a preferred embodimentof the present invention in detail. Those of skill in the art willrecognize that there are numerous variations and modifications of thisinvention that are encompassed by its scope. Accordingly, thedescription of a preferred embodiment should not be deemed to limit thescope of the present invention.

The term “degradable” as used herein is a broad term, and is to be givenits ordinary and customary meaning to a person of ordinary skill in theart (and is not to be limited to a special or customized meaning), andrefers without limitation to a process by which structural integrity ofthe balloon is compromised (e.g., by chemical, mechanical, or othermeans (e.g., light, radiation, heat, etc.) such that deflation occurs.The degradation process can include erosion, dissolution, separation,digestion, disintegration, delamination, comminution, and other suchprocesses.

The term “swallowable” as used herein is a broad term, and is to begiven its ordinary and customary meaning to a person of ordinary skillin the art (and is not to be limited to a special or customizedmeaning), and refers without limitation to ingestion of a balloon by apatient such that the outer capsule and its constituents are deliveredto the stomach via normal peristalsis movement. While the systems ofpreferred embodiments are swallowable, they are also configured byingestion by methods other than swallowing. The swallowability of thesystem is derived, at least in part, by the outer container size for theself-inflating system and the catheter and outer container size for themanual inflation system. For the self-inflating system, the outercapsule is sufficient to contain the inner container and itsconstituents, an amount of activation agent injected prior toadministration, the balloon size and the balloon material thickness. Thesystem is preferably of a size less than the average normal esophagusdiameter.

Described herein is an orally ingestible device. In preferredembodiments, the device is able to traverse the alimentary canal. Thedevice may be useful, for example, as an intragastric volume-occupyingdevice. The device overcomes one or more of the above-described problemsand shortcomings found in current intragastric volume-occupying devices.

In order to more clearly describe the subject matter of the preferredembodiments, different embodiments of the same subcomponent will bedescribed under a single relevantly-titled subheading. This organizationis not intended to limit the manner in which embodiments of differentsubcomponents may be combined in accordance with the present invention.

Swallowable Intragastric Balloon System

A swallowable, self-inflating or inflatable intragastric balloon systemaccording to selected preferred embodiments includes the followingcomponents: self-sealing valve system for addition of fluid to the lumenof the balloon or to the inner container (“valve system”), a balloon ina deflated and compacted state (“balloon”) and an outer capsule,container, or coating (“outer container”) that contains the balloon. Forself-inflating balloons, an inner capsule or other container (“innercontainer”) that contains one or more CO₂ generating components ispresent inside the lumen of the balloon. For inflatable balloons, aninflation fluid source, a catheter and tubing (“inflation assembly”) areprovided for inflating the balloon after ingestion or placement in thestomach. In the self-inflating balloon configuration, the valve ispreferably attached to the inner surface of the balloon by an adhesiveor other means (e.g., welding), and provided with an inoculation spacerto prevent puncture of the wall of the balloon and inner container by aneedle or other means for injecting an liquid activation agent into thelumen of the balloon via the self-sealing valve. A valve providingreleasable attachment of the tubing to the balloon is provided in theinflatable balloon configuration. Preferably, the self-sealing valvesystem attached to the balloon (e.g., on its inside surface) in theinflatable configuration is “universal” or compatible with a swallowablecatheter or a physician-assisted catheter. The valve system serves toallow for balloon inflation using a miniature catheter that includes aneedle assembly and also provides a mechanism for detachment of thecatheter after inflation has been completed.

The outer container preferably incorporates the balloon in a compactedstate (e.g., folded and rolled), preferably with sufficient space toallow for activation liquid to be injected into the balloon in theself-inflating balloon configuration, wherein the liquid activationagent initiates separation, erosion, degradation, and/or dissolution ofthe inner container and generation of CO₂ upon contact with theinflation agent contained within the inner container, which subsequentlycauses outer container separation, erosion, degradation, and/ordissolution due to CO₂ gas pressure. In the inflatable balloonconfiguration, the outer container need only incorporate the balloon ina compacted state.

Selected components of a swallowable intragastric balloon system of apreferred embodiment can include a silicone head with radioopacity ring,trimmed 30 D silicone septum, Nylon 6 inoculation spacer, compactedballoon, inner container (if self-inflating), and outer container asconstituents of the system in unassembled form. A fully assembled outercontainer can include a vent hole aligned with a septum for puncture toinject liquid activation agent (if self-inflating) or a port forconnection of tubing (if inflatable). As discussed further below, thecomponents of particularly preferred systems possess the attributesdescribed herein; however, in certain embodiments systems can beemployed which utilize components having other attributes and/or values.

Devices according to the preferred embodiments are intended foringestion by a patient and deployment without the need to resort toinvasive methods. It is therefore desirable that the device of thepreferred embodiments be operable to conform to a compact delivery statewhich can be swallowed by a patient with minimal discomfort. Once in thestomach, it is desirable for the device to assume a substantially largerdeployed state. In order to achieve the transition from a delivery stateto a deployed state the device is subjected to inflation.

Inner Container

In order to initiate inflation in the self-inflating configuration, theinflation subcomponent may require outside inputs such as an activationagent. The activation agent is preferably injected using a syringehaving a needle with a gauge diameter of from 25 to 32. The needlelength is preferably from about 0.25 inches (0.6 cm) to 1 inches (2.54cm) in length so as to create a flow rate that allows for delivery ofthe full volume of inflation agent within 30 seconds, but in amanner/stream/flow that does not physically damage the inner container,thereby causing premature CO₂ generation and inflation. The activationagent is preferably pure water, or a solution containing up to 50%concentration of anhydrous citric acid at 20° C., or the equivalentthereof at varying solution temperatures based on solubility ofanhydrous citric acid. Preferably, the system is configured to have anoccupyable void space in the central lumen of the balloon when incompacted form in the outer container of from about 0.3 ml to about 4.5ml, such that a corresponding volume of activation agent can be injectedinto the void space.

In one embodiment, prior to folding, the free-floating inner containerwith inflation agent for CO₂ generation is preferably vertically alignedwith the self-sealing valve system such that the septum/inoculationspacer is placed directly above the tip of the capsule. The ballooncontains an inner container. A self-sealing valve system is adhesivelyadhered to the interior of the wall of the balloon, and the invertedconfiguration of the balloon is provided by inversion through a holesealed with a patch. The top approximate ¼ of the balloon wall is foldedover the inner capsule, and the pleats where the capsule is are creasedsimilar to the pleats formed in the second step of making a paperairplane, then folded over to the left or to the right. The bottomapproximate ¾ of the sphere is then accordioned using no more than 2creases and folded over the capsule. The left half is then folded overthe right half of the capsule or vice versa so that the wings touch.Then the material is rolled over until it creates a tight roll. Thedevice is then placed inside the outer container.

In a self-inflating configuration, the balloon is folded so as to form apocket around the inner capsule, to insure that the liquid injectedthrough the self-sealing valve system is contained in an area less than10% of the entire balloon surface area. It is not necessary to provide apocket in the inflatable configuration, as no inner capsule is provided.The balloon is folded such that the number of total folds is minimizedso as to minimize possible damage to the outer material or compromise ofbarrier properties. The number of total folds is preferably less than 10folds. The balloon material is rolled when at all possible such that thenumber of creases required to fit the balloon in an outer container isminimized. This is done in effort to also to prevent lumen materialdamage. The self-sealing valve is also preferably constructed off-centerof the balloon so as to minimize the number of folds that layer on topof each other.

In the self-inflating configuration, the material forming the wall ofthe balloon is processed and folded to maximize reaction efficiency bylocalizing the initiation agent injected into the balloon so that it ismaintained proximal to the reactants within the inner container. Theballoon is folded such that once the reaction initiates and the outercontainer separates, the balloon unfolds in a manner that creates thelargest possible surface area, which prohibits the balloon from readilypassing through the pyloric sphincter. The ratio of reactants in theinflation agent and activation agent are selected such that the pH ofany remnant liquid inside the lumen of the balloon is acidic, with a pHof less than 6, such that any balloon leakage or breach that allowsstomach acid to enter does not cause additional CO₂ generation andresulting unintentional re-inflation.

In a self-inflating configuration, an inflation agent is compressed,formed or otherwise held in a shape which provides good surface areaavailability for the reactants for CO₂ generation, while minimizing thespace and/or volume sufficient to hold the inner container. Preferably,the inner container has a length (longest dimension) of from about 0.748inches (1.9 cm) to 1.06 inches (2.7 cm) and a diameter or width of fromabout 0.239 inches (0.6 cm) to about 0.376 inches (1 cm). The volume ofthe inner container is preferably from about 0.41 ml to about 1.37 ml.The inner container is preferably in the form of a standard push-fitgelatin capsule but a gelatin tape may be used in lieu of a push-fitcapsule. The container is preferably relied upon for containing theinflation agent; however, additional sealing or other encapsulation canbe employed to control timing of inflation. Gelatin is particularlypreferred for use as the inner container; however other materials canalso be suitable for use, e.g., cellulose. In order to minimize theinternal volume of the system, it is generally preferred to include onlya single inner container; however, in certain embodiments two or moreinternal containers can advantageously be employed. Timing ofself-inflation is selected based on a normal esophageal transit time anda normal time of gastric emptying of large food particles, such that theballoon does not inflate to a size that can block the esophagealpassageway or prematurely pass through the pyloric sphincter. Timing isalso controlled by compacting the balloon such that the activation agentis substantially localized in the balloon next to the inner capsule,creating an efficient CO₂ self-inflation method. Balloon inflation isinitiated by the liquid activation agent causing degradation of theinner container, such that the inflation agent in the inner containercontacts the liquid activation agent, thereby initiating the gasgeneration reaction.

Inflation Assembly

In certain preferred embodiments, the volume-occupying subcomponent isfilled with a fluid using tubing which is subsequently detached andpulled away from the volume-occupying subcomponent. One end of thevolume-occupying subcomponent has a port connected to tubing ofsufficient length that when unwound can span the entire length of theesophagus, from mouth to stomach. This tubing is connected to thevolume-occupying subcomponent with a self-sealable valve or septum thatcan tear away from the volume-occupying subcomponent and self-seal oncethe volume-occupying subcomponent is inflated. A physician or otherhealth care professional secures one end of the tubing as the patientswallows the device. Once the device is residing within the stomach, thephysician uses the tube to transmit a fluid, such as air, other gas(es),saline solution, pure water, or the like, into the volume-occupyingsubcomponent and thereby inflate it. After the volume-occupyingsubcomponent is fully inflated, the tubing is released and can be pulledout from inside the patient.

The tube may be released in a number of manners. For example, the tubingmay be detached by applying a gentle force, or tug, on the tubing.Alternatively, the tubing may be detached by actuating a remote release,such as a magnetic or electronic release. Additionally, the tubing maybe released from the volume-occupying subcomponent by an automaticejection mechanism. Such an ejection mechanism may be actuated by theinternal pressure of the inflated volume-occupying subcomponent. Forexample, the ejection mechanism may be sensitive to a specific pressurebeyond which it will open so as to release any excess pressure andsimultaneously release the tube. This embodiment provides a desirablefeature through combining release of the tubing with a safety valve thatserves to avert accidental over inflation of the volume-occupyingsubcomponent in the patient's stomach.

This automatic release embodiment also provides the benefit that thedevice inflation step may be more closely monitored and controlled.Current technology allows for a self-inflating intragastricvolume-occupying subcomponent which generally begins to inflate in afour minute timeframe after injection with an activation agent such ascitric acid. In this approach, the volume-occupying subcomponent may, insome instances, begin to inflate prior to residing within the stomach(e.g., in the esophagus), or, in patients with gastric dumping syndromeor rapid gastric emptying, the volume-occupying subcomponent may end upin the small intestine prior to the time that inflation occurs.Accordingly, in certain embodiments it can be desirable to inflate thevolume-occupying subcomponent on command, once it is ascertained thatthe volume-occupying subcomponent is residing in the correct location.

In certain embodiments, it may also be advantageous for thevolume-occupying subcomponent to inflate gradually or in several stepsover time. For example, if gas escapes the volume-occupying subcomponentprior to the desired deflation time, it can be beneficial for the deviceto re-inflate in order to preserve it in its expanded state.

Outer Container

The balloon is preferably provided in a deflated and folded state in acapsule or other retaining, containing or coating structure (“outercontainer”). The outer container is preferably in the form of a standardpush-fit gelatin capsule, with the push-fit relied upon for containingthe deflated/folded balloon; however, a gelatin wrap can advantageouslybe employed in certain embodiments. Gelatin is particularly preferredfor use as the outer container; however other materials can also besuitable for use, e.g., cellulose, collagen, and the like. Preferably,the outer container has a length (longest dimension) of from about 0.95inches (2.4 cm) to 2.5 inches (6.3 cm) and a diameter or width of fromabout 0.35 inches (0.9 cm) to about 0.9 inches (2.4 cm). The volume ofthe inner container for the self-inflatable version is preferably fromabout 1.2 ml to about 8.25 ml. In the self-inflating configuration, theouter container is preferably configured with one or more holes, slits,passageways or other egresses, preferably on each end, which can act asvents such that any gas created due to inflation agent exposure tocondensation or other ambient moisture present during processing doesnot cause premature separation or degradation of the inner containerprior to 30 seconds after inoculation of the liquid activation agent,which may have an undesirable effect on reaction efficiency. Suchegresses can also expedite dissolution of the outer container to preparethe balloon for inflation in the inflatable configuration. The processof the outer capsule degrading (e.g., separates, dissolves, or otherwiseopens) is expedited by pressure build up caused by inflation(self-inflation or inflation via catheter) of the balloon. The outercapsule can be dipped in water for a brief time to soften the materialsbut not release the balloon prior to swallowing to minimize the timelapse between swallowing and balloon inflation. In the inflatableconfiguration, the outer container is provided with a hole to house theinflation tube needle assembly, wherein the diameter of the catheterneedle housing is mechanically compatible with the diameter of the outercontainer hole such that the needle can be inserted into theself-sealing valve while maintaining therein the housed balloon tofacilitate pushing or swallowing of the balloon assembly. In a preferredembodiment, the outer container is a capsule. The distal half of thecapsule may be flared to prevent abrasion of the balloon materials bythe leading edge of the capsule as the compacted balloon is insertedinto the capsule. The capsule can also comprise two parts held togetherwith a gel band and encompassing the folded balloon that allows forquicker separation of the capsule so that inflation can take place moreexpeditiously. The outer capsule degrades (e.g., separates, dissolves,or otherwise opens) due to contact with ingested fluid ingestion (e.g.,water intake) and preferably degrades within 5 minutes or less, morepreferably within 2 minutes or less, so as not to cause discomfort tothe patient while the balloon/catheter tube is in place.

In a preferred embodiment, the device is fitted into a standard sizedgelatin capsule. The capsule may be formed of a material that has aknown rate of degradation such that the device will not be released fromthe capsule or otherwise deployed prior to entry into the stomach. Forexample, the capsule materials may include one or more polysaccharideand/or one or more polyhydric alcohols.

Alternatively, the device, in its delivery state, may be coated in asubstance that confines the device in its delivery state while alsofacilitating swallowing. The coating may be applied by a dipping,sputtering, vapor deposition, or spraying process which may be conductedat an ambient or positive pressure. The balloon may also be encapsulatedby wrapping gelatin tape around the balloon and then placing the wrappedballoon in a capsule, if so desired.

In certain preferred embodiments, the encapsulated or coated device islubricated or otherwise treated so as to facilitate swallowing. Forexample, the encapsulated or coated device may be wetted, heated, orcooled, prior to swallowing by the patient. Alternatively, theencapsulated or coated device may be dipped in a viscous substance thatwill serve to lubricate the device's passage through the esophagus.Examples of possible coatings can be any substances with lubriciousand/or hydrophilic properties and include glycerine,polyvinylpyrrolidone (PVP), petroleum jelly, aloe vera, silicon-basedmaterials (e.g. Dow 360) and tetrafluoroethylene (TFE). The coating mayalso be applied by a sputtering, vapor deposition or spraying process.

In additional embodiments the coating or capsule is impregnated ortreated with one or more local anesthetics or analgesics to easeswallowing. Such anesthetics may include anesthetics in the amino amidegroup, such as articaine, lidocaine and trimecaine, and anesthetics inthe amino ester group, such as benzocaine, procaine and tetracaine. Suchanalgesics may include chloraseptic.

In certain embodiments, the capsule may be weighted at a certain end inorder for it to be oriented appropriately when it is administered, as ittravels down the esophagus, and/or when it is in the stomach. Theweighting components may include polymer materials or inflationreactants.

The swallowable, self-inflating intragastric balloon is provided withmechanisms to reliably control timing of self-inflation such thatpremature inflation while in the esophagus during swallowing is avoidedand sufficient inflation once in the stomach so as to prevent passagethrough the pyloric sphincter is ensured. Normal esophageal transit timefor large food particles has been documented as 4-8 seconds, and gastricemptying of large food particles through the pylorus does not occur forat least 15-20 minutes. The outer container is preferably configured toseparate, dissolve, degrade, erode, and/or otherwise allow thedeflated/folded balloon to begin unfolding not less than 60 seconds butnot more than 15 minutes after inoculation with liquid activation agent.The inner container is preferably configured chemically, mechanically ora combination thereof to retard the initial CO₂ generating chemicalreaction such that sufficient CO₂ to begin inflating the balloon is notavailable earlier than 30 seconds after inoculation with the liquidactivation agent, but to permit generation of sufficient CO₂ such thatat least 10% of the occupyable volume of the balloon is filled within 30minutes, at least 60% of the occupyable volume of the balloon is filledwithin 12 hours, and at least 90% of the occupyable volume of theballoon is filled within 24 hours. This timing allows for injection ofthe activation agent into the outer container by the medicalprofessional, passing the device to the patient, and swallowing bynormal peristaltic means by the patient. This timing also prohibitspotential passing of an uninflated balloon into the duodenum by theballoon being inflated to a sufficient size such that gastric emptyingof the balloon cannot be easy, as objects more than 7 mm in diameter donot readily pass.

Delivery Components

It certain embodiments, it may advantageous for an administrator of thedevice to use a delivery tool for delivering the device to the mouth orfacilitating its passage through the esophagus in the optimalorientation. A delivery tool may enable the device administrator toinject the device with one or more inflation agents as the device 10 isbeing administered to the patient. In a preferred embodiment, suchinjection may be accomplished in the same mechanical action(s) of theadministrator that are employed to release the device from the deliverytool into the mouth or esophagus. For example, the delivery tool mayinclude a plunger, a reservoir having a liquid, and an injection needle.The administrator pushes the plunger which, either in sequence orapproximately simultaneously, forces the injection needle into thedevice and thereby injects the liquid contained in reservoir into thedevice. Subsequent application of force to the plunger pushes the deviceout of the delivery tool and into the desired location within thepatient. Furthermore, the delivery tool may also include a subcomponentthat administers an anesthetic or lubricant into the patient's mouth oresophagus to ease the swallowability of the device.

Balloon

The volume-occupying subcomponent (“balloon”) of the preferredembodiments is generally formed of a flexible material forming a wallwhich defines an exterior surface and an interior cavity. Various of theabove-described subcomponents may be either incorporated into the wallor interior cavity of the volume-occupying subcomponent. As shown,volume-occupying subcomponent can vary in size and shape according tothe patient's internal dimensions and the desired outcome. Thevolume-occupying subcomponent may be engineered to be semi-compliant,allowing the volume-occupying subcomponent to stretch or expand withincreases in pressure and/or temperature. Alternatively, in someembodiments, a compliant wall offering little resistance to increases involume may be desirable.

Spherical volume-occupying subcomponents are preferred in certainembodiments. Alternatively, the volume-occupying subcomponent may beconstructed to be donut-shaped, with a hole in the middle of it, and maybe weighted and shaped in such a way that it orients in the stomach tocover all or part of the pyloric sphincter, similar to a check valve.The hole in the middle of the volume-occupying subcomponent can thenserve as the primary passage for the contents of the stomach to enterthe small intestine, limiting the passage of food out of the stomach andinducing satiety by reducing gastric emptying. Volume-occupyingsubcomponent may be manufactured with different-sized donut-holesaccording to the degree that gastric emptying is desired to be reduced.Delivery, inflation and deflation of the volume-occupying subcomponentmay be accomplished by any of the methods described above.

It is advantageous in certain embodiments for the volume-occupyingsubcomponent wall to be both high in strength and thin, so as tominimize the compacted volume of the device as it travels the esophagusof the patient. In certain embodiments, the volume-occupyingsubcomponent wall materials are manufactured with a biaxial orientationthat imparts a high modulus value to the volume-occupying subcomponent.

In one embodiment, the volume-occupying subcomponent is constructed of apolymeric substance such as polyurethane, polyethylene terephthalate,polyethylene naphthalate, polyvinyl chloride (PVC), Nylon 6, Nylon 12,or polyether block amide (PEBA). The volume-occupying subcomponent maybe coated with one or more layers of substances that modify (increase,reduce, or change over time) gas-barrier characteristics, such as athermoplastic substance.

Preferably, the gas-barrier materials have a low permeability to carbondioxide or other fluids that may be used to inflate the volume-occupyingsubcomponent. The barrier layers should have good adherence to the basematerial. Preferred barrier coating materials include biocompatiblepoly(hydroxyamino ethers), polyethylene naphthalate, polyvinylidenechloride (PVDC), saran, ethylene vinyl alcohol copolymers, polyvinylacetate, silicon oxide (SiOx), acrylonitrile copolymers or copolymers ofterephthalic acid and isophthalic acid with ethylene glycol and at leastone diol. Alternative gas-barrier materials may includepolyamine-polyepoxides. These materials are commonly acquired as asolvent or aqueous based thermosetting composition and are generallyspray-coated onto a preform and then heat-cured to form the finishedbarrier coating. Alternative gas-barrier materials which may be appliedas coatings to the volume-occupying subcomponent include metals such assilver or aluminum. Other materials that may be used to improve the gasimpermeability of the volume-occupying subcomponent include, but are notlimited to, gold or any noble metal, PET coated with saran, conformalcoatings and the like, as listed, for example, in Tables 1a-b.

In certain preferred embodiments, the volume-occupying subcomponent isinjection, blow or rotational molded. Either immediately following suchmolding, or after a period of curing, the gas-barrier coating may beapplied if not already applied within the composite wall.

In another embodiment, the intragastric volume-occupying subcomponent isformed using a Mylar polyester film coating silver, aluminum orkelvalite as a metallicized surface, to improve the gas impermeabilityof the volume-occupying subcomponent.

In the event that the volume-occupying subcomponent's wall is composedof multiple layers of materials, it may be necessary to use certainsubstances or methods to connect, attach or hold together such multiplelayers. Such substances can include a solvent or an ether-basedadhesive. Such multiple layers may also be heat-bonded together. Oncesuch layers are attached together to form (for example) a sheet ofmaterial to be made into a volume-occupying subcomponent, it may also benecessary to apply additional treatment steps to such material to allowit to seal together (for example, by application of a certain degree ofheat and pressure) in order to be made into a volume-occupyingsubcomponent. Accordingly, it may be advantageous to include as anadditional layer in the volume-occupying subcomponent certain materialsthat seal. For example, a volume-occupying subcomponent comprised of acombination of PET and SiOx layers, which impart favorable mechanicaland gas impermeability characteristics to the volume-occupyingsubcomponent, may be sealed by including a layer of sealablepolyethylene in such volume-occupying subcomponent.

According to another embodiment of the preferred embodiments, thefunctionality of the volume-occupying subcomponent and the deflationcomponent is combined either in part or in whole. For example, thevolume-occupying subcomponent may be formed of a substance that isdegraded within the stomach over a desired period of time. Once thedegradation process has formed a breach in the wall of thevolume-occupying subcomponent, the volume-occupying subcomponentdeflates, continues to degrade and passes through the remainder of thedigestive tract.

Preferably, an automated process is employed that takes a fullyconstructed volume-occupying subcomponent, evacuates all of the airwithin the interior cavity and folds or compresses the volume-occupyingsubcomponent into the desired delivery state. For example, theevacuation of air from the volume-occupying subcomponent may be actuatedby vacuum or mechanical pressure (e.g. rolling the volume-occupyingsubcomponent). In certain embodiments, it is desirable to minimize thenumber of creases produced in the volume-occupying subcomponent when inthe delivery state.

In another embodiment, deflation of the volume-occupying subcomponentmay be achieved through one or more injection site within the wall ofthe volume-occupying subcomponent may be achieved through one or moreinjection sites within the wall of the volume-occupying subcomponent.For example, two self-sealing injection sites can be incorporated atopposite sides of the volume-occupying subcomponent. Thevolume-occupying subcomponent may be positioned within a fixture thatemploys two small-gauge needles to evacuate the air from thevolume-occupying subcomponent.

In one embodiment, the self-sealing injection sites may further be usedto insert chemical elements of the inflation subcomponent into theinterior of the volume-occupying subcomponent. After injection of thechemical elements into the volume-occupying subcomponent, the sameneedles may be used to perform evacuation of the volume-occupyingsubcomponent.

It may be desirable that the volume-occupying subcomponent is packedinto the delivery state under, for example, a negative vacuum pressureor under a positive external pressure.

The volume-occupying subcomponent wall materials may also be engineeredto, once they are initially punctured or torn, tear relatively easilyfrom the point of such puncture or tear. Such properties can, forexample, be advantageous if deflation of the volume-occupyingsubcomponent were initiated by a tearing or puncturing of thevolume-occupying subcomponent wall, since such initial tear or puncturemay then increase in scope, hastening and/or maximizing the deflationprocess.

The volume-occupying subcomponent may also be coated by a lubricioussubstance that facilitates its passage out of the body following itsdeflation. Examples of possible coatings can be any substances withlubricious and/or hydrophilic properties and include glycerine,polyvinylpyrrolidone (PVP), petroleum jelly, aloe vera, silicon-basedmaterials (e.g. Dow 360) and tetrafluoroethylene (TFE). The coating maybe applied by a dipping, sputtering, vapor deposition or sprayingprocess which may be conducted at an ambient or positive pressure.

The balloon composite wall materials can be of similar construction andcomposition as those described in U.S. Patent Publication No.2010-0100116-A1, the contents of which is hereby incorporated byreference in its entirety. The materials are able to contain a fluid,preferably in compressed or non-compressed gas form, such as, e.g., N₂,Ar, O₂, CO₂, or mixture(s) thereof, or atmospheric air (composed of amixture of N₂, O₂, Ar, CO₂, Ne, CH₄, He, Kr, H₂, and Xe) that simulategastric space concentrations. In certain embodiments, the balloon isable to hold the fluid (gas) and maintain an acceptable volume for up to6 months, preferably for at least 1 to 3 months after inflation.Particularly preferred fill gases include non-polar, large moleculegases that can be compressed for delivery.

Prior to placement in the outer container, the balloon is deflated andfolded. In the inverted configuration in a deflated state, the balloonis flat, with the inverted seam extending around the perimeter of theballoon. The self-sealing valve system is affixed to the inner wall ofthe lumen close to the center of the deflated balloon, with the innercontainer positioned adjacent to the self-sealing valve system. Thewalls of the balloon are then folded. As part of the balloon design, theself-sealing valve system is manufactured in a manner such that it canbe and is preferably placed “off center” to minimize the number of foldsupon themselves (e.g., doubling or tripling up) required to fit theballoon in the outer container. For example, the self-sealing valvesystem can advantageously be placed ½ r±¼ r from the center of theballoon, wherein r is the radius of the balloon along a line extendingfrom the center of the balloon through the septum.

Tracking and Visualization Subcomponent

It may also be beneficial to implement tracking and visualizationfunctionality into devices according to the present inventions. Due tothe non-invasive nature of the present device, physicians may desire todetermine, or confirm, the location and orientation of the device priorto inflation or during the course of treatment.

Alternatively, the marker may be applied to the volume-occupyingsubcomponent when the volume-occupying subcomponent is in a creased orfolded state such that when the volume-occupying subcomponent is in itsdeflated state the marker appears concentrated when viewed onvisualization equipment, and when the volume-occupying subcomponent isinflated the marker appears less concentrated when viewed onvisualization equipment. Alternatively, the marker may be applied orincorporated into the volume-occupying subcomponent so as to facilitateidentification and location of the various subcomponents of the device,such as a valve, head, or weight. The marker may be printed or paintedonto a surface of the volume-occupying subcomponent or between layers ofthe material forming the volume-occupying subcomponent. Alternatively, ametal coating as described below may be used as a marker to identifyand/or locate the volume-occupying subcomponent. Metal coatings forvisualizing the volume-occupying subcomponent may include silver, gold,tantalum or any noble metal. Alternatively, the marker may be applied toan elastomeric sleeve that covers all or part of the volume-occupyingsubcomponent.

In another embodiment, the volume-occupying subcomponent incorporates asubcomponent that changes mechanically upon inflation of thevolume-occupying subcomponent, which mechanical change can be visualizedusing x-ray or other visualization equipment. For example, a mechanicalportion of the volume-occupying subcomponent containing a visualizationmarker may elongate upon an increase in pressure in the volume-occupyingsubcomponent.

Alternatively, a marker may be formed using a metallized mesh locatedbetween layers of the material from which the volume-occupyingsubcomponent is constructed. The pattern or patterns formed by theimbedded marker will appear when the volume-occupying subcomponent is inan inflated, deployed state.

It is envisioned that marker materials may be incorporated into thevolume-occupying subcomponent to facilitate various visualizationtechniques such as, for example, MRI, CT and ultrasound.

The volume-occupying subcomponent may also contain a dye or marker thatis released upon deflation to indicate that the volume-occupyingsubcomponent cavity has been breached. Such dye or marker may, forexample, be apparent in the patient's urine as an indication that thevolume-occupying subcomponent has begun to deflate.

In yet further embodiments, microchips and other components employingelectronic modalities may be used to locate and identify a device.Microchips analogous to those utilized for the identification of petsmay be used to communicate device specific information and itsapproximate location. For example, a Wheatstone or other bridge circuitmay be incorporated into the device and, together with RF “ping andlisten” technology may be used as part of a system to determine thedevice's approximate location and measure and communicate devicespecific information. Such device specific information can includeinternal volume-occupying subcomponent pressure, which can indicate thedegree of inflation of the volume-occupying subcomponent.

In yet further embodiments, mechanical, chemical, visual and othersensors may be included as part of the device to measure, record and/ortransmit information relating to the device and/or the patient'sinternal environment. For example, the device may contain a camera orany of the other imaging and transmission components of a Pillcamdevice. As an additional example, the device may contain sensors thatmeasure, record and/or transmit information relating to stomach pH,stomach pressure, hormone levels, organ health, and organ safety.

Valve System

In preferred embodiments, a self-sealing valve system is attached to theballoon (e.g., on its inside surface) that is “universal” or compatiblewith the swallowable catheter and a physician-assisted catheter. Thevalve system serves to allow for balloon inflation using a miniaturecatheter that includes a needle assembly and also provides a mechanismfor detachment of the catheter after inflation has been completed. FIGS.1A-D depict views representing a design of a self-sealing valve systemwhich contains a self-sealing septum housed within a metallic concentriccylinder is provided. In the inflatable configuration, the self-sealingvalve system is preferably adhered to the underside of the balloonmaterial such that only a portion of the valve protrudes slightlyoutside of the balloon surface to ensure a smooth surface. The valvesystem for the inflatable configuration can utilize the sameself-sealing septum designed for the self-inflating configuration. Theseptum preferably consists of a material possessing a durometer of 20Shore A to 60 Shore D. The septum is inserted or otherwise fabricatedinto the smaller cylinder of the concentric metallic retaining structure(FIGS. 2A-D) that is preferably cylindrical in shape. The smallercylinder within the larger cylinder controls alignment of the catheterneedle sleeve/needle assembly with the septum, provides a hard barrierso that the catheter needle does not pierce the balloon material (needlestop mechanism), and provides compression such that the valve/septumre-seals after inflation and subsequent needle withdrawal.

The concentric valve system can also provide radio opacity duringimplantation and is preferably titanium, gold, stainless steel, MP35N(nonmagnetic, nickel-cobalt-chromium-molybdenum alloy) or the like.Non-metallic polymeric materials can also be used, e.g., an acrylic,epoxy, polycarbonate, nylon, polyethylene, PEEK, ABS, or PVC or anythermoplastic elastomer or thermoplastic polyurethane that is fabricatedto be visible under x-ray (e.g., embedded with barium).

The septum can be cone shaped, so that the compressive forces aremaximized for self-sealing after inflation. The self-sealing septumallows air to be evacuated from the balloon for processing/compactingand insertion into the outer container, and allows for piercing by aninflation agent syringe needle (self-inflating configuration) orinflation catheter needle (inflatable configuration), and thensubsequent withdrawal of the inflation agent syringe needle ordetachment of the inflation catheter and withdrawal of the catheterneedle significantly limiting gas leakage outside of the balloon duringthe inflation process and needle withdrawal/catheter detachment. Theseptum is inserted into the valve using a mechanical fit mechanism toprovide compression. An additional ring (FIGS. 3A-C) can be placed atthe distal end of the inner cylinder to provide additional compressionto ensure the septum material is pre-loaded so as to re-seal itself. Thering is preferably metallic in nature, but can also be a non-metallicpolymeric material such as an acrylic, epoxy, or thermoplastic elastomeror thermoplastic polyurethane. The ring material is preferably the samematerial as the cylinder, titanium, but can also be gold, stainlesssteel, MP35N or the like.

In an inflatable configuration, a larger, outer cylinder (FIGS. 4A-D) ofthe concentric valve housing contains a slightly harder durometermaterial than the inner cylinder (50 Shore A or greater), but is alsopreferably silicone. The purpose of using a harder durometer material isto ensure sealing when connected to the needle sleeve for inflation. Thesilicone located in the outer ring of the concentric valve is adhered tothe balloon from the inside surface. The entire outer cylinder is filledand a small circular lip of this same material is provided that isslightly larger than the diameter of the inner cylinder and extends tothe outside surface of the balloon. The lip is compatible with the bellshaped needle sleeve and provides sealing to enhance connection of thevalve to the catheter to withstand the inflation pressures applied andalso increases the ejection distance or attachment force of thecatheter. This silicone lip preferably does not protrude past theballoon surface more than 2 mm to ensure that the balloon surfaceremains relatively smooth and does not cause abrasion or ulcerations ofthe mucosa. It is designed to provide compressive forces against theneedle sleeve of the catheter for inflation and detachment whereby whenconnected to the needle sleeve of the inflation catheter, the connectioncoupling can preferably withstand a pressure of 35 PSI during inflation.The seal is then broken during detachment using hydraulic pressure thatis preferably more than 40 PSI but less than 200 PSI to separate thecoupling. An additional retaining ring (FIGS. 5A-C) preferably made ofthe same material as concentric valve, can be included in the valvesystem to further enhance the seal between the metal and the valvesilicone and provide additional mechanical support to ensure propermechanical fit and are intended to disrupt slippage of the siliconematerial from the hard (metallic) valve system (causing an increase intensile force).

The valve structure for the inflatable configuration uses a mechanicalfit mechanism to provide the functions of the self-sealable valve forinflation by the catheter and subsequent catheter detachment; however,primer and/or adhesive may be used to provide additional support inconstruction of the assembly. The configuration can be modified bymodifying the surfaces of the metal components, making them more stickyor slippery e.g. more or less conducive to adhesion, to provide thedesired mechanical/interference fit. The interference fit between thevalve and the catheter can be modified to change the pressurerequirements for inflation and/or detachment. Additional assemblies caninclude overmolding the metallic portions or the concentric system insilicone such that additional support rings to ensure the mechanical fitand the tensile strength and forces required to sustain the assemblyduring catheter inflation and detachment can be omitted.

The total valve diameter in the inflatable configuration is designed tofit a miniature catheter system that does not exceed 8 French (2.7 mm,0.105 inches) in diameter. The total diameter does not exceed 1 inch(2.54 cm) and is preferably less than 0.5 inches (1.27 cm), tofacilitate swallowing. Additional valves can be added, if desired;however, it is generally preferred to employ a single valve so as tomaintain the volume of the deflated/folded balloon (and thus the outercontainer dimensions) as small as possible. The valve system ispreferably attached to the balloon and bonded such that a shear forcegreater than 9 lbs (40 N) is required to dislodge the valve system.

In a self-inflating configuration, the valve system can be attached tothe balloon (e.g., on its inside surface) without the use of an opening,orifice, or other conduit in the wall of the balloon. The valve systemcan utilize a septum with a durometer of 20 Shore A to 60 Shore D. Thevalve can be inserted or otherwise fabricated into a retaining structurethat has a higher durometer, e.g., 40 Shore D to 70 Shore D or more. Theretaining structure can be fabricated from a silicone, rubber, softplastic or any suitable non-metallic polymeric material such as anacrylic, an epoxy, a thermoplastic elastomer, or thermoplasticpolyurethane. Preferably, a structure, such as a ring, that can bemetallic or non-metallic but radio opaque (e.g., barium) and visibleunder X-ray, can be embedded in the retaining structure. Using amechanical fit mechanism of two structures of different durometers, onesofter (septum) with a large diameter, can be inserted into a snug, ahigher durometer structure creates compressive forces in the once openorifice to enable CO₂ retention and reduce susceptibility for CO₂ gasleaks. The metallic ring for radio-opacity also helps to supportcompressive forces on the septum. The self-sealing septum allows air tobe evacuated from the balloon for processing/compacting and inserting inthe outer container, and also allows for the inflation agent to beinjected into the outer container for inflation initiation. Additionalseptums can be provided, if desired; however, it is generally preferredto employ a single septum so as to minimize the volume of thedeflated/folded balloon (and thus the outer capsule) to as small aspossible. The valve system is preferably attached to the inside of theballoon such that a shear force greater than 9 lbs (40 N) is required todislodge the valve system. A silicone head and radio opaque ring of aself-sealing valve system can be employed, as can a wedge-shaped septum.

In the self-inflating configuration, an inoculation spacer is preferablyincorporated to guide a needle into the self-sealing valve for injectionof liquid activation agent into the lumen of the balloon and to preventthe needle from penetrating the wall of the deflated/folded balloonelsewhere such that pressure within the lumen of the balloon cannot bemaintained. The inoculation spacer also facilitates preventing liquidactivation agent from penetrating the inner container or the foldedballoon material, thereby focusing the activation agent in anappropriate manner to properly mix the reactants for CO₂ generationaccording to the criteria described above. The inoculation spacer isgenerally in the form of a tube or cylinder. The inoculation spacer ispreferably attached to the inner container and/or the self-sealing valvesystem with an adhesive or other fixing means; however, in certainembodiments the inoculation spacer can be “free-floating” and maintainedin position by the folding or rolling of the walls of the balloon. Theinoculation spacer can comprise any suitable material that can be passedafter separation, erosion, degradation, digestion, and/or dissolution ofthe outer container; however, preferable materials include non-metallicmaterials with a minimum Shore D durometer of 40 or more, any metallicmaterial, or a combination thereof. A cupped needle stop (inoculationspacer) can be employed in preferred embodiments.

Balloon

In a preferred embodiment, a self-inflating balloon is fully sealed 360degrees around. In the self-inflating configuration, with injection ofan inflation agent by needle syringe, there are preferably no externalopenings or orifices to the central lumen. In the inflatableconfiguration, a valve structure (either protruding, recessed, or flushwith the surface of the balloon) is provided for providing an inflationfluid to the central lumen. The balloon can have a “noninverted”,“inverted”, or “overlapped” configuration. In a “noninverted”configuration, the seams or welds and seam allowance, if any, are on theoutside of the inflated balloon. In an “overlapped” configuration,layers are overlapped, optionally with one or more folds, and secured toeach other via welds, a seam, adhesive, or the like, resulting in asmooth external surface. In an “inverted” configuration, the balloon hasa smooth external surface with seams, welds, adhesive bead, or the likeinside the inflated balloon. In order to create a balloon with aninverted configuration, e.g., a balloon with no external seam allowance(no wall material between the edge of the balloon and the weld, seam, orother feature joining the sides together), two balloon halves are joinedtogether in some fashion (e.g., adhered using adhesive or heat or thelike based on the balloon material used). One of the balloon halvesencompasses an opening to allow for the balloon to be pulled throughitself after adherence of the two halves and to have the seams of theballoon on the inside. The opening created is preferably circular butcan be any similar shape, and the diameter of the opening preferablydoes not exceed 3.8 cm; however, in certain embodiments a largerdiameter may be acceptable. A patch of material is adhered (adhesively,heat welded, or the like, based on the material used) to cover theoriginal balloon-half opening. The inversion hole thus created that issubsequently patched is small enough that the forces exerted duringinflation do not compromise the material used to maintain fluid in theballoon. The preferred shape for the inflated balloon in final assemblyis ellipsoid, preferably spheroid or oblate spheroid, with nominal radiiof from 1 inch (2.5 cm) to 3 inches (7.6 cm), a nominal height of from0.25 inches (0.6 cm) to 3 inches (7.6 cm), a volume of from 90 cm³ to350 cm³ (at 37° C. and at internal nominal pressure and/or fullinflation), an internal nominal pressure (at 37° C.) of 0 psi (0 Pa) to15 psi (103421 Pa), and a weight of less than 15 g. The self-inflatingballoon is configured for self-inflation with CO₂ and is configured toretain more than 75% of the original nominal volume for at least 25days, preferably for at least 90 days when residing in the stomach. Theinflatable balloon is configured for inflation with an appropriatemixture of gases so as to deliver a preselected volume profile over apreselected time period (including one or more of volume increaseperiods, volume decrease periods, or steady state volume periods).

The preferred shape for the inflated balloon in final assembly isellipsoid, preferably spheroid or oblate spheroid, with nominal radii offrom 1 inch (2.5 cm) to 3 inches (7.6 cm), a nominal height of from 0.25inches (0.6 cm) to 3 inches (7.6 cm), a volume of from 90 cm³ to 350 cm³(at 37° C. and at internal nominal pressure and/or full inflation), aninternal nominal pressure (at 37° C.) of 0 psi (0 Pa) to 15 psi (103421Pa), and a weight of less than 15 g. In certain embodiments wherein astable volume over the useful life of the device is preferred, theballoon is configured to maintain a volume of at least 90% to 110% ofits original nominal volume. In other embodiments, it can be desirablefor the balloon to increase and/or decrease in volume over its usefullife (e.g., in a linear fashion, in a stepwise fashion, or in anothernon-linear fashion).

Inner Container

The inner container for the self-inflating balloon is contained withinthe lumen of the balloon and contains the CO₂ generator for balloonself-inflation. The CO₂ generator comprises an inflation agent mixturehoused within the container. Preferably, from about 10% to about 80% ofthe total inflation agent used comprises powdered citric acid, with theremainder comprising powdered sodium bicarbonate. Sufficient inflationagent is provided such that upon completion of the CO₂ generatingreaction, the balloon achieves inflation at the nominal inflationpressure described above. Preferably, a total of from about 0.28 to 4grams inflation agent mixture is employed, depending upon the balloonsize to be inflated; preferably up to 1.15 grams of sodium bicarbonateis used with the remainder being powdered citric acid to generate 300cm³ of CO₂ at nominal pressure.

Inflation Assembly

An intragastric balloon system that is manually inflated by a miniaturecatheter can be employed in certain embodiments. The system preferablyremains “swallowable.” The balloon for delivery is in a compacted stateand is attached to a flexible, miniature catheter, preferably no largerthan 4 French (1.35 mm) in diameter. The catheter is designed such thata portion of the catheter can be bundled or wrapped upon itself fordelivery with the encapsulated balloon, allowing the patient to swallowboth catheter and balloon for delivery to the stomach. The balloon cancontain a self-sealable valve system for attachment of the catheter andinflation of the balloon once it reaches the stomach cavity. Theproximal end of the catheter can be left just outside of the patient'smouth, permitting connection to an inflation fluid container that canhouse the preferred inflation fluid (gas or liquid). After inflation thecatheter can be detached from the balloon valve and pulled back throughthe mouth. This method allows for the intragastric balloon to maintainits swallowability but allow for inflation by a fluid source or amixture of fluid sources via the catheter. Alternatively, a more rigid,pushable system can be employed wherein the balloon valve is compatiblewith either the swallowable, flexible catheter or the pushable, rigidcatheter assembly.

The inflation catheters (swallowable or administrator-assisted pushable)described herein are configured to deliver the balloon device orally andwithout any additional tools. The administration procedure does notrequire conscious sedation or other similar sedation procedures orrequire endoscopy tools for delivery. However, other versions of thedevice can be used in conjunction with endoscopy tools for visualizationor can be adapted such that the balloon device can be deliverednasogastrically as well.

In operation, the proximal end of the inflation catheter is connected toa valve or connector that allows for connection to the inflation sourceor the disconnect source, this is preferably a connector or inflationvalve (FIG. 6 and FIG. 7, respectively). The connector materials mayconsist of polycarbonate or the like and can connect to a single ormulti-lumen catheter tube. The distal end of the inflation catheter isconnected to the universal balloon valve of the balloon that has beencompacted and housed within a gelatin capsule or compacted using gelatinbands (FIG. 8A-B). The catheter tube is preferably from 1 French (0.33mm) to 6 French (2 mm) in diameter. The catheter is preferably longenough to extend out past the mouth (connected to the inflationconnector or valve) and transverse the esophagus down to at least themiddle of the stomach—approximately 50-60 cm. Measurement ticks can beadded to the tubing or catheter to aid in identifying where the end ofthe tube is located. Timing for inflation can be initiated by having thetube contain a pH sensor that determines a location difference betweenthe esophagus (pH 5-7) and the stomach (pH 1-4) based on the differentpH between the two anatomical sources, or can be derived or verifiedfrom the expected pressure in a contained (i.e., esophagus) versus aless-constrained space (i.e., stomach). The tube can also containnitinol that has a tunable transmission to the body temperature, takinginto account the timing for swallowing. The tube can also be connectedto a series of encapsulated or compacted balloons on a single catheter.Each can be inflated and released separately. The number of balloonsreleased can be tune-able to the patient's needs and desired weightloss.

In certain embodiments, a catheter with the balloon at the distal end(inflated with air) is employed to temporarily and firmly hold theballoon in place. A small deflated balloon catheter can be positionedthrough the head of the gastric balloon (e.g., a “balloon within theballoon”), and then inflated with air during delivery to firmly hold thecapsule and balloon in place and prevent spontaneous detachment ofballoon from the catheter. This balloon catheter can incorporate a dualchannel that can also allow the bigger gastric balloon to be inflated(by gas or liquid). Once the gastric balloon has been satisfactorilyinflated, the small air balloon catheter can be deflated and pulled outof the valve (allowing the valve to self seal), and out of the body,leaving the inflated gastric balloon in the stomach.

In other embodiments, the catheter may be coated to enhanceswallowability or is impregnated or treated with a flavored versionand/or one or more local anesthetics or analgesics to ease swallowing.Such anesthetics may include anesthetics in the amino amide group, suchas articaine, lidocaine and trimecaine, and anesthetics in the aminoester group, such as benzocaine, procaine and tetracaine. Suchanalgesics may include chloraseptic.

Dual Lumen Catheter

In a preferred embodiment, a swallowable dual lumen catheter isprovided. The dual lumen catheter (FIGS. 9A-C) has two lumens with adiameter of the complete assembly no larger than 5 French (1.67 mm),preferably no larger than 4 French (1.35 mm). The inner lumen preferablydoes not exceed 3 French (1 mm) and functions as the inflation tube, andthe outer lumen preferably does not exceed 5 French (1.67 mm) andfunctions as the disconnection tube. The catheter assembly is connectedto a needle assembly, described in more detail below, at the distal endand to a dual port inflation connector at the proximal end. The tubingthat the catheter assembly employs is flexible for swallowability, iskink resistant, can withstand body temperature, is resistant to acid,and is biocompatible as the tube transverses the alimentary canal intothe stomach cavity. The tube materials are preferably soft and flexibleand have moderate tensile strength and a significant amount of hoopstrength to handle applied pressures. The lumens are preferably roundand co-axial and free-floating so as to provide flexibility. The duallumen assembly also preferably requires no adhesive or glue. Alternativelumen configurations can include two D-lumens or a combination of aD-lumen and round lumen, and can be used in stiffer configurations ofthe final catheter assembly. Preferred materials for the tubing includea thermo-resistant polyethylene tubing such as PEBAX® or a thermoresistant polyurethane tubing such as PELLETHANE™, PEEK or Nylon. Thetubing can also be manufactured out of bioresorbable materials such aspolylactic acid (PLA), poly-L-aspartic acid (PLAA), polylactic/glycolicacid (PLG), polycaprolactone (PCL), DL-lactide-co-ε-caprolactone(DL-PLCL) or the like, wherein the tube can be released after inflationand detachment and swallowed as normal.

At the distal end of the catheter assembly, the inner lumen or inflationtube is attached to the needle assembly that is used to puncture theballoon's self-sealing valve, preferably located at one of the apexes ofthe balloon housed inside of a gelatin capsule as outer container. Theouter lumen is connected to the needle sleeve and provides connectionforce between the catheter assembly and balloon providing the tensilestrength to withstand starting inflation pressures of preferably up to10 psi and preferably no more than 35 PSI while maintaining the assemblytogether. The needle sleeve is configured to mechanically couple withthe balloon valve assembly. The needle is preferably made of metal,preferably stainless steel or the like, with a maximum size of 25 gauge(0.455 mm), preferably no smaller than 30 gauge (0.255 mm) for inflationtiming purposes. The needle sleeve is preferably a soft material such asnylon or the like, or can also be polycarbonate, polyethylene, PEEK, ABSor PVC. The needle sleeve covers the length of the needle in itsentirety, such that the body is protected from the needle and the needlecan only pierce the balloon septum. Preferably the needle sleeve isflush or extends out slightly more than the needle length. The needle isinserted into the balloon septum prior to swallowing and maintains aretention force of approximately 0.5 lb when coupled to the siliconearea of the balloon valve. The needle sleeve is preferably slightly bellshaped (FIGS. 10A-D) or contains a circular relief or lip so that wheninserted into the silicone area of the valve a lock and key mechanism iscreated to increase the tensile strength of the assembly and enhance thesealing for inflation.

At the proximal end, the catheter assembly is connected to a Y-adapterassembly preferably made of polycarbonate. The y-adapter is “keyed” sothat the inflation gas and connection fluid are connected to thecatheter assembly appropriately and travel down the correct lumen.

Prior to inflation, priming of the disconnection lumen may be employedusing a liquid. For example, the outer lumen is first flushed with 2 ccof water, saline, DI water or the like prior to balloon inflation.Thereafter, the inflation source container is attached to the connectorleading to the inner lumen. The inflation source container works on thepremise of the ideal gas law and a pressure decay model. For a givencompressed gas formulation, the device is designed to equalize such thata higher starting pressure is used to inflate the balloon than is theresulting end pressure of the balloon. The starting pressure and volumeare dependent upon the gas formulation selected, as well as the lengthof the catheter and the starting temperature (typically ambienttemperature) and ending temperature (typically body temperature).

After inflation, the balloon is detached from the catheter assemblyusing hydraulic pressure. A syringe filled with water, DI water, orpreferably saline is attached to the female end of the Y-assembly. Thesyringe contains 2 cc of liquid and when the syringe plunger is pushedin, enough hydraulic pressure is exerted such that the needle is ejectedfrom the balloon valve.

Single Lumen Catheter

To further reduce the diameter of the inflation catheter, therebyincreasing swallowability comfort of the balloon capsule and catheter, asingle lumen catheter (FIG. 11A-C) can be employed that does not exceed3 French (1.0 mm) in diameter (0.033 inches).

The needle/needle sleeve assembly is similar in design to that of thedual lumen catheter described herein. However, with the single lumensystem, the distal end of the catheter lumen connects to the needlesleeve only and there is no second catheter inside. Instead, a singlethread attached to a needle hub runs co-axially the length of thecatheter to aid in tensile strength for detachment and overallflexibility.

The needle sleeve is slightly bell shaped or contains a circular reliefor lip so that when inserted into the silicone head of the valve a lockand key mechanism is created to increase the tensile strength of theassembly, enhance the sealing for inflation, and since this is a singlelumen assembly, the lip increases the force required to remove theneedle from the valve so this does not occur haphazardly during theinflation process.

The proximal end of the catheter is connected to an inflation valve(FIG. 7), preferably a 3-way valve, or any valve that allows for using amethod of exclusion for inflation and detachment of the balloon. Thedistal end of the catheter contains the needle sleeve, which is made ofnylon or other similar source. The needle is metallic and preferablystainless steel.

The tubing that the catheter assembly employs is flexible forswallowability, is kink resistant, can withstand body temperature, isresistant to acid, and is biocompatible as the tube transverses thealimentary canal into the stomach cavity. The tube materials arepreferably soft and flexible and resistant to necking or buckling orkinking. For a single lumen system, the catheter tubing is preferablymade of PEBAX® or PELLETHANE® (an ether-based polyurethane elastomer),but can also comprise bioresorbable materials such as PLA, PLAA, PLG,PCL, DL-PLCL or the like, wherein the tube can be released afterinflation and detachment and swallowed as normal. The threadlike wire(FIG. 11 B) inside the catheter tubing attached to the needle ispreferably a nylon monofilament, but Kevlar or nitinol wire or othersuitable materials can also be used.

To inflate the balloon, the distal end of the catheter is attached tothe balloon capsule where the needle protrudes through the self-sealablevalve (FIG. 11C). The container is swallowed and a portion of theinflation catheter remains outside of the mouth. The inflation sourcecontainer is connected to the proximal end of the inflation valve, wherethe port for inflation gas is chosen by excluding the other ports. Theinflation fluid (preferably compressed nitrogen gas or a mixture ofgases) travels down the single catheter lumen, whereby the inflation gasselects the path of least resistance, or more specifically through theneedle cavity and into the balloon. The balloon is preferably inflatedin less than 3 minutes.

To detach and withdraw the needle from the balloon valve, 2 cc or othersuitable volume of water or other liquid is injected into the catheterat a high pressure. Since water has a high surface tension andviscosity, it occludes the needle pathway and the pressure istransferred to the outside needle sleeve, thereby breaking the fitbetween the needle sleeve and the balloon valve.

If it is desired to place a substance inside the balloon, such as wateror acid or any alternative liquid, it can be done by using a lowerpressure to inject the liquid.

Miniature Stiff-Bodied Inflation Catheter

In certain embodiments, a stiff-bodied inflation catheter can beemployed, which can be placed orally or trans-nasally. This system canbe from 1 French (0.33 mm) to 10 French (3.3 mm), preferably 8 French(2.7 mm) in diameter. A larger diameter is typically preferred toenhance pushability, with wall thickness also contributing topushability and kink resistance. The length of the tube can beapproximately 50-60 cm. As discussed above, measurement ticks can beadded to the tubing to identify where the end of the tube is located, ora pH or pressure sensor on the catheter can be employed to detectlocation of the balloon.

This system for inflation/detachment is similar to the dual lumen systemdescribed above, but with a larger needle sleeve to accommodate thelarger diameter tube (FIGS. 12A-D). Materials that can be used in thelumen include, e.g., expanded polytetrafluoroethylene (EPTFE) for theouter lumen and polyetheretherketone (PEEK) for the inner lumen. To alsoenhance pushability, a strain relief device can be added to the distaland proximal ends. It is particularly preferred to have strain relief atthe distal end, e.g., 1 to 8 inches, preferably 6 inches, to ensure thecatheter bypasses the larynx and follows into the esophagus. Theproximal end can have strain relief as well, e.g., to ensure fit of theconnector. The preferred material for the strain relief is a polyolefin.The method for inflation/detachment is the same method as for the duallumen configuration where the outer lumen connects to the needle sleeveand the inner lumen connects to the needle. Stiffening members arestrategically placed along the length of the catheter shaft to providethe correct amount of flexibility and pushability to properly place thedevice in the patient. As part of the procedure, the patient can swallowwater or other suitable liquid so as to distend esophageal tissue forsmooth passage down of the device. Patients can also be administered ananesthetic at the back of the throat to numb the area and lessen the gagreflex.

The tube can also be connected to a series of encapsulated or compactedballoons on a single catheter such that a total volume of up to 1000 ccor more can be administered, as necessary. Each can be inflated andreleased separately. The number of balloons released can be tunable tothe patient's needs and desired weight loss.

In addition, a catheter can be used for administering a gastric balloonthat is similar to balloon catheters used in angioplasty termed“over-the-wire” or rapid exchange catheters (FIG. 13). In this casewhere the patients attempts to swallow the catheter but fails so thestiff catheter—or physician assisted catheter can slide over theflexible catheter and the balloon can be pushed down in the same manneras the physician-assisted catheter. Different materials can be used toprovide the varying degrees of flexibility or one material that isfabricated with different diameters across the length to vary the degreeof stiffness can be used.

Inflation Fluid Container

The inflation fluid container is employed to control the amount orvolume of fluid placed inside of the balloon. This can be in the form ofa canister of, e.g., PVC, stainless steel, or other suitable material.The container can also be in syringe form. The materials employed areable contain a fluid, preferably in gas form, e.g., compressed ornon-compressed N₂, Ar, 0 ₂, CO₂, or mixture(s) thereof, or compressed ornon-compressed atmospheric air (a mixture of N₂, 0 ₂, Ar, CO₂, Ne, CH₄,He, Kr, H₂, and Xe). The balloon composite wall materials and respectivediffusion gradients and gas permeability characteristics are used toselect a fluid for inflation of the intragastric balloon. The InflationFluid container materials are selected to ensure there is no diffusionor leakage of the fluid before it is connected to the connector or valveof the inflation catheter. The inflation fluid container system (FIGS.14A-C) includes a connector (FIG. 14B) to the catheter and a pressuregauge (FIG. 14C). The inflation fluid container can be fabricated fromany suitable material, e.g., stainless steel (FIG. 15). It can alsocontain a smart chip that notifies the healthcare professional ofwhether inflation is successful or if the balloon should be detached dueto an error in the system.

To maintain “swallowability” of the balloon and to ensure comfort of thepatient during the procedure, it is preferred to minimize the amount oftime the catheter is placed in the mouth/esophagus. Timing of inflationis can be selected so as to minimize time in place. The outercontainer-catheter assembly, once swallowed, takes approximately 4-8seconds to reach the stomach. Once in the stomach, the Inflation sourcecontainer can be attached to the valve or port of catheter system.Inflation timing can be controlled by selecting the length of catheter,diameter of the catheter tube, the starting temperature, and thestarting pressure. Using the Ideal Gas Law for nitrogen and Boyle's Law(P₁V₁=P₂V₂) the amount of starting volume/pressure can be derived, wheretemperature is controlled inside the inflation source container to matchthat of the body. It is desired to have an inflation time after swallowof less than 5 minutes, and preferably 2-3 minutes, before balloondetachment and catheter withdrawal. The inputs use to derive inflationof the balloon (preferably in less than 3 minutes) include inflationcontainer volume, type of inflation fluid (preferably a compressed gasor compressed gas mixture), starting pressure, catheter length anddiameter, and desired end volume and pressure of the balloon. Thus, dueto differences in diameter, a 2 French catheter system requires a higherstarting pressure to achieve the same target balloon volume and pressurein the same time frame, assuming use of the same compressed gasformulation. In general, it is understood that starting with a higherpressure with the same flow rate/volume can decrease the inflation time.

The inflation source container provides feedback to the end user basedon a pressure decay system. Where there is an expected starting pressureand expected ending pressure to indicate whether the balloon is inflatedproperly, there is no need for endoscopic visualization (see FIG. 16).Each scenario of expected pressure outputs depicted in FIG. 16 can haveits own tolerances around it to reduce possibilities of false positives,and the inflation fluid container can provide feedback based on thesetolerances as to the status of balloon inflation and detachment. This isderived based on the Ideal Gas Law, where there is an expected endpressure based on the fixed volume of the balloon. If the pressureremains high and doesn't decay as expected, this can indicate a failurein the system (e.g., the balloon container did not dissolve, the balloonis expanding in the esophagus because there is, e.g., a kink in the tubeor other failure in the catheter system). For example, for a successfuldecay using nitrogen only as the inflation fluid, the starting pressureis 22 PSI to inflate a balloon to 250 cc and 1.7 psi (0.120 kg/cm²) fora nylon-based material. To indicate successful balloon inflation, a mathchip can be added to the inflation source container that provides atleast one of a visual, audible, or tactile notification, or otherwisetransmits a notification to a healthcare professional or administratorof whether inflation is successful or if there is an error in the systembased on the pressure curve and a set of predetermined pressuretolerances and expected timing of inflation.

Alternatively, the balloon can be filled based on a starting pressure byusing a spring mechanism, a balloon-within-balloon mechanism, or otherpressure source. These mechanisms can potentially result in morepredictable/consistent pressure decay curves, and again can haveaccompanying, predetermined tolerances for feedback back to the enduser. FIG. 17 depicts the expected decay curve for these methods ofpressure sources, and again would have accompanying, predeterminedtolerances for feedback back to the end user.

Composite Wall

The materials selected for the composite wall of the balloon may beoptimized to maintain the original inflation gas without significantdiffusion, or may also allow for diffusion of the gases located in thegastric environment, e.g., CO₂, O₂, argon, or N₂ to diffuse through thewall of the balloon to inflate, partially or wholly, once the balloon isplaced in the stomach. A fluid (a liquid or gas) can also be addedinside of the balloon using the inflation catheter(s) described hereinto change diffusion direction of the balloon composite wall and when itreaches stasis based on the internal and external environment.

A gastric balloon inflated by nitrogen, CO₂ gas, a single fluid (gas) ora mixture of gasses employs a composite wall that provides barrierproperties (fluid retention), properties imparting resistance to pH andmoisture conditions in the gastric environment or the environment withinthe central lumen of the balloon, and structural properties to resistgastric motility forces, abrasion of the balloon wall in vivo, anddamage during manufacturing and folding of the balloon. Certainmaterials employed in the balloon materials are able to withstand ahostile gastric environment designed to break down foreign objects(e.g., food particles). Some of the variables that the gastricenvironment encompasses are as follows: gastric liquid pH of from 1.5-5;temperature of approx. 37° C.; a relative humidity of 90-100%; ingressof gastric space gas content; and constant gastric motility externalpressures of from 0-4 psi at variable frequencies and cycle times basedon the fed state of the stomach. The external pressure imparted bygastric motility can also cause abrasions on the surface of the balloon.The inside of the balloon lumen may contain moisture from a solutioninjected in the balloon for timing of auto-deflation or any moisturethat has transferred across the membrane due to the external humidenvironment. In addition to these environmental stresses the wallmaterials meet biocompatibility requirements and are constructed suchthat the total thickness of the wall (barrier material) is thin enoughto be compacted and placed inside of a swallowable-sized container(“outer container”) without significant damage or lodging. The outercontainer is small enough to transcend the esophagus (which has adiameter of approximately 2.5 cm). The wall or barrier material is alsoheat formable and sealable for balloon construct and maintains a bondstrength that can contain internal gas pressures of up to 10 psigenerated by the initial inflation pressure as well as pressure due tothe ingress of gas molecules from the stomach cavity until the system'sgas environment reaches stasis. The film properties that are evaluatedto determine suitability for use in the composite wall of the ballooninclude pH resistance, water vapor transmission rate, gas barrierproperties, mechanical strength/abrasion properties, temperatureresistance, formability, flex-crack (Gelbo) resistance, surface energy(wettability) compliance, and heat bond potential.

The various layers in the composite wall can impart one or moredesirable properties to the balloon (e.g., fluid retention, resistanceto moisture, resistance to acidic environment, wettability forprocessing, and structural strength). A list of polymer resins andcoatings that can be combined into a multi-layer preformed system(“composite wall”) is provided in Tables 1a-b. These films can beadhesively bonded together, co-extruded, or adhered via tie layers or acombination thereof to obtain the desired combination of properties forthe composite wall, as discussed below. The materials identified as filmcoatings in Tables 1a-b are provided as coatings applied to a basepolymer film, e.g., PET, Nylon, or other structural layer.

TABLE 1a Film Resins Characteristics Good Good Fluid GoodStructural/Behavior/ Retention Manufacturability/ Mechanical BarrierSurface Strength/Compliance Properties Energy Properties FILM RESINSPolyethylene X X Terephthalate (PET) Polytrimethylene Terephthalate(PTT) Liquid Crystal Polymer X X (LCP) Polytrimethylene X X naphthalate(PTN) Polyethylene X X naphthalate (PEN) Polyimide (PI) X X Linear LowDensity X Polyethylene (LLDPE) Ethylene Vinyl Alcohol X (EVOH)Polyamide:Nylon X X (PA) and Nylon-6 (PAG)/Nylon 12 High Density XPolyethylene (HDPE) Polypropylene (PP) X Polyurethane X PVDC (Saran) X XPolyether Block Amide X (Pebax) Polyvinyl Alcohol X (PVOH) Silicone X X

TABLE 1b Film Coatings Characteristics Good Good Fluid GoodStructural/Behavior/ Retention Manufacturability/ Mechanical BarrierSurface Strength/Compliance Properties Energy Properties FILM COATINGSSilicone Dioxide X (SiO2) Aluminum Oxide X (Al₂O₃) Nanopolymers X(Nano/Clay) External Organic X Coatings (e.g., epoxy amine) InorganicCoatings X (e.g., Amorphous Carbon) Oxygen Scavengers X Parylene C X

Fluid Retention Layers

In preferred embodiments, a blended polymer resin using multiple layersis employed to maintain the inflated balloon's shape and volume byretaining the inflation fluid for the duration of the intended use.Certain barrier films, widely used in the food packaging and plasticbottling industries, can advantageously be employed for this purpose inthe composite wall of the balloon. Preferably, the barrier materialshave a low permeability to carbon dioxide (or other gases, liquids, orfluids that are alternatively or additionally used to inflate thevolume-occupying subcomponent). These barrier layers preferably havegood adherence to the base material. Preferred barrier coating materialsand films include polyethylene terephthalate (PET), linear low densitypolyethylene (LLDPE), ethylene vinyl alcohol (EVOH), polyamides such asNylon (PA) and Nylon-6 (PA-6), polyimide (PI), liquid crystal polymer(LCP), high density polyethylene (HDPE), polypropylene (PP),biocompatible poly(hydroxyamino ethers), polyethylene naphthalate,polyvinylidene chloride (PVDC), saran, ethylene vinyl alcoholcopolymers, polyvinyl acetate, silicon oxide (SiOx), silicon dioxide(SiO₂), aluminum oxide (Al₂O₃), polyvinyl alcohol (PVOH), nanopolymers(e.g., nanoclay), polyimide thermoset film, EVALCA EVAL EF-XL, HostaphanGN, Hostaphan RHBY, RHB MI, Techbarrier HX (SiOx-coated PET), TriadSilver (silver metallized PET), Oxyshield 2454, Bicor 84 AOH,acrylonitrile copolymers, and copolymers of terephthalic acid andisophthalic acid with ethylene glycol and at least one diol. Alternativegas-barrier materials include polyamine-polyepoxides. These materialsare typically provided as a solvent-based or aqueous-based thermosettingcomposition and are typically spray-coated onto a preform and thenheat-cured to form the finished barrier coating. Alternative gas barriermaterials that can be applied as coatings to the volume-occupyingsubcomponent include metals such as silver or aluminum. Other materialsthat may be used to improve the gas impermeability of the volumeoccupying subcomponent include, but are not limited to, gold or anynoble metal, PET coated with saran, and conformal coatings.

One method that is used in the packaging industry to delay diffusion ofthe inflation fluid is to thicken the material. Thickening the materialis generally not preferred, as the total composite wall thicknesspreferably does not exceed 0.004 inches (0.010 cm) in order for theballoon to be foldable into the desired delivery container size forswallowing by a patient.

A multilayer polymer film that is able to withstand the gastricenvironment over the course of the usable life of the balloon includeslinear low density polyethylene (LLDPE) adhesively bonded to a Nylon 12film. Alternatively, an additional film layer with barrier properties,such as PVDC can be added to the composite wall.

The layers providing gas barrier properties are preferably situated asinner layers in the composite wall as they are less mechanically robustthan resins that are considered “structural” such as Nylon and the like.

Structural Layers

Layers such as polyurethane, Nylon, or polyethylene terephthalate (PET)can be added to the composite wall for structural purposes, and arepreferably placed as outermost (proximal to the gastric environment orproximal to the central lumen of the balloon) layers, provided that thepH resistance of such layers can withstand the acidic environment of thestomach or the central lumen of the balloon.

Fabrication of the Composite Wall

The various layers of the composite wall, including the gas barrierlayers, need not be situated in any particular order, but those ofsuperior resistance to acidity, temperature, mechanical abrasion, andsuperior biocompatibility profile are preferably employed as layerscontacting the gastric environment. Those with superior resistance to,e.g., acidity and temperature, are preferably employed as layerscontacting the central lumen of the balloon.

The various layers of the wall can include a single layer or up to 10 ormore different monolayers; however, a film thickness of from 0.001inches (0.0254 cm) to 0.004 inches (0.010 cm) thick is desirable suchthat the resulting balloon compacted to fit into a swallowable capsule.The resulting composite wall preferably has good performancespecifications with respect to each category listed in Tables 1a-b.

Films that are co-extruded are advantageously employed, as someadhesives may contain leachables that are undesirable from abiocompatibility perspective. In addition, coextrusion allows for betterblending such that the materials maintain their original properties whencombined in this fashion and are less likely to be subject todelamination when exposed to gastric motility forces.

Combining films with similar properties, e.g., two film layers withexcellent gas barrier properties, in a composite wall is advantageousfor use in a gastric balloon containing nitrogen, oxygen, CO₂ or amixture thereof as the inflation gas or where the external environmentthe product is to be placed in, contains a mixture of gases includingCO₂, e.g., the stomach. A primary advantage of such composite films isthat restrictions on film thickness can be observed without sacrifice ofgas barrier properties. Such a configuration also contributes toreducing the effects of processing damage (e.g., manufacturing andcompacting) and damage due to exposure to in vivo conditions (e.g.,gastric motility forces).

In a particularly preferred embodiment, the composite wall includes aplurality of layers. The first layer is an outer protective layer thatis configured for exposure to the gastric environment. This layer isresistant to mechanical forces, exposure to water (vapor), abrasion, andhigh acidity levels. Nylon or more specifically, Nylon 12 isparticularly preferred for the layer exposed to the gastric environment,and is especially resistant to mechanical forces.

In an alternative embodiment, polyurethane is RF welded to saran toyield a 6-7 mil thick composite wall. In another embodiment, a fivelayer system is provided comprising a layer of saran sandwiched betweentwo polyurethane layers. Between the saran layer and each of thepolyurethane layers is a tie layer. The layers can be welded together,co-extruded or adhered using an adhesive. This tri-layer is thenco-extruded to Nylon on each side, and then a final sealing layer(polyethylene or the like) is added to one of the nylon layers for thetotal composite wall. A representative example of material combinationsthat are commercially available or manufacturable is provided in Table2. The orientation of the layers (innermost—in contact with the centralballoon lumen, or outermost—in contact with the gastric environment) isalso indicated if more than two layers are described to support asuggested composite wall.

Most of the film resins listed in Table 2 provide some degree of gasbarrier properties. Therefore, many can be used solely to form theballoon wall as a monolayer film; however they can also be used inconjunction with other film resins to meet the desired gas retention andmechanical specifications for the useful life of the balloon based onthe inflation gas and external environment the balloon is to be placedin. These film resins can also be coated with gas barrier coatingslisted in Tables 1a-b. Additional film layers can be added to form thetotal composite wall. While such additional layers may not impartsubstantial barrier properties, they can provide structural and/ormechanical properties, protection for the other layers of the compositewall that are susceptible to water vapor, humidity, pH, or the like, orother desirable properties. The film layers can be assembled usingvarious adhesives, via co-extrusion, via lamination, and/or using tielayers and such to create a composite wall that meets the requirementsof an intragastric balloon suitable for use for at least 25 days, or upto 90 days or more, with the specified gas retention properties. Table 2provides a list of layers and layer combinations suitable for use incomposite walls for an intragastric balloon. The composite description,resin abbreviation, configuration (single layer, bilayer, trilayer, orthe like) and trade name of commercially available combinations arelisted. The number of layers indicated does not include any adhesivelayers or tie layers used to fabricate the composite wall, such that a6-layer composite wall may, for example, have two or three adhesivelayers and/or tie layers that make up the total composite wall, andtherefore the total number of layers can be eight or nine in final form.The term “layer” as used herein is a broad term, and is to be given itsordinary and customary meaning to a person of ordinary skill in the art(and is not to be limited to a special or customized meaning), andrefers without limitation to a single thickness of a homogenoussubstance (e.g., a coating such as SiOx, or a layer such as PET), aswell as to a supporting layer having a coating thereon (wherein a“coating” is, e.g., a material typically employed in conjunction withsubstrate that provides structural support to the coating layer). Forexample, a PET-SiOx “layer” is referred to herein, wherein a layer ofSi-Ox is provided on a supporting PET layer.

TABLE 2 Example Film Composite Walls* Abbreviation Trade namepolyethylene terephthalate PET Mylar metallized oriented polyethylenemetallized OPET Custom terephthalate polyvinyl alcohol coated orientedPVOH coated OPP Bicor polypropylene metallized biaxially oriented nylon6 metallized OPA6 Custom Biaxally oriented Nylon/ethylene OPA/EVOH/OPAHoneywell vinyl alcohol/biaxally oriented Nylon Oxyshield PlusNylon/ethylene vinyl alcohol/Low Nylon/EVOH/LDPE Custom DensityPolyethylene polyvinylidene chloride coated PVDC/OPET Mylar orientedpolyethylene terephthalate polyvinylidene chloride coated PVCD/OPPCustom oriented polypropylene polyvinylidene chloride coated PVCD/OPA6Honeywell biaxally oriented Nylon 6 Oxyshield high densitypolyethylene/ethylene HDPE/EVOH Custom vinyl alcoholpolypropylene/ethylene vinyl PP/EVOH Custom alcohol laminatepolyethylene PET/EVOH Custom terephthalate/ethylene vinyl alcoholmetallized oriented polypropylene metallized OPP Custom sealable PVDCcoated oriented PVDC coated PP Custom polypropylene polyvinylidenefluoride PVDF Custom Polyvinyl chloride PVC Custom polyvinyl fluoridePVF Tedlar polychlorofluoroethylene PCTFE ACLAR UltRx, SupRx, Rxamine-based epoxy coated Nylon epoxy coated PA6 Bairocade polyvinylchloride-polyvinylidene PVC-PVDC Custom chloride copolymer mediumdensity polyethylene MDPE Custom Nylon/Polypropylene Nylon/PP laminateCustom Nylon-High Density Polyethylene Nylon-HDPE laminate Custom Nylon12/Ethyl Methyl Co-extruded Nylon 12- Custom Co- Acrylate/PolyvinylideneChloride/ encapsulated PVDC-Nylon 12- extruded blend Ethyl MethylAcrylate/Nylon LLDPE + LDPE 12/Linear Low Density Polyethylene + LowDensity Polyethylene Multi-layer Nylon 12/Linear Low Co-extrudedmulti-layer Custom Co- Density Polyethylene + Low Nylon 12- ExtrudedBlend Density Polyethylene LLDPE + LDPE acetylene plasma coating onPET/A Custom polyester difluoroethylene coating on PET/DA Custompolyethylene terephthalate oriented polypropylene OPP Custom castpropylene CPP Custom high density polyethylene HDPE Custom cyclic olefincopolymer COC Custom oriented polystyrene OPS Custom FluorinatedEthylene Propylene FEP Custom difluoroethylene coating on low LDPE/DCustom density polyethylene difluoroethylene coating on PP/D Custompolypropylene acetylene plasma coating on PP/A Custom polypropyleneacetylene plasma coating on low LDPE/A Custom density polyethylenepolybutylene terephthalate TPC-ET Hytrel polyether glycol copolymerpolyether block amide TPE PEBA Pebax oxide coated biaxally orientedoxide coated PA Honeywell Nylon Oxyshield Ultra Nanoclay/nylonMXD6/Nanoclay Imperm/Aegis OXCE Polyethylene PET/SiOx BestPET/Terephthalate/Silicone Dioxide TechBarrier Polyethylene PET + 02Scavengers MonoxBar Terephthalate/Oxygen scavengers ModifiedPolyethylene Modified PET DiamondClear Terephthalate PolyethyleneTerephthalate/Nylon 6 PET/MXD6 HP867 Amorphous polyvinyl alcoholAmorphous PVOH Nichigo G- Polymer Nylon 6/Ethyl vinyl Nylon 6/EVOH/LLDPECustom alcohol/Linear Low Density Polyethylene Ethyl vinyl alcohol/Poly-EVOH/PP/EVOH Custom Propylene/Ethyl vinyl alcohol Ethyl vinylalcohol/Nylon EVOH/Nylon Custom Polyethylene/Ethyl vinyl PE/EVOH/PECustom alcohol/Polyethylene Polyethylene/Ethyl vinyl alcohol/PE/EVOH/PET Custom Polyethylene Terephthalate Silicon dioxide-coatedPET-SiOx/LLDPE/EVOH/LLDPE Custom Polyethylene Terephthalate/Linear LowDensity Polyethylene/Ethyl vinyl alcohol/Linear Low Density PolyethyleneAluminum Oxide-coated PET-Al₂O₃/LLDPE Custom PolyethyleneTerephthalate/Polyethylene Polyethylene/Ethyl vinyl PE/EVOH/LLDPE Customalcohol/Linear Low Density Polyethylene Polyethylene Terephthalate/PET/PE/OEVOH/PE Custom Polyethylene/Polyethylene/Bi- axially orientedEthyl vinyl alcohol Polyethylene Terephthalate/ PET/PE/EVOH/EVOH/EVOH/PECustom Polyethylene/Ethyl vinyl alcohol/ Ethyl vinyl alcohol/Ethyl vinylalcohol/Polyethylene Polyethylene Terephthalate/ PET/PE/Nylon6/EVOH/Nylon Custom Polyethylene/Nylon 6/Ethyl vinyl 6/PE alcohol/Nylon6/Polyethylene Silicone dioxide-coated PET-SiOx/PE/EVOH/PE CustomPolyethylene Terephthalate/ Polyethylene/Ethyl vinyl alcohol/Polyethylene Polyethylene/Ethyl vinyl PE/EVOH/PVDC Customalcohol/polyvinylchloride Polyethylene Terephthalate/LinearPET/LLDPE/EVOH/LLDPE Custom Low Density Polyethylene/Ethyl vinylalcohol/Linear Low Density Polyethylene Kurrarister C-coatedPolyethylene PET-Kurrarister-C/PE/EVOH/PE CustomTerephthalate/Polyethylene/Ethyl vinyl alcohol/Polyethylene PolyethyleneTerephthalate/ PET/PE/Nylon 6/EVOH/Nylon Custom Polyethylene/Nylon6/Ethyl vinyl 6/PE alcohol/Nylon 6/Polyethylene Nylon 6/Ethyl vinylalcohol/ Nylon 6/EVOH/PVDC/Nylon Custom Polyvinylchloride/Low Density6/LDPE Polyethylene Polyimide PI Custom Polyimide/Linear Low DensityPI/LLDPE Custom Polyethylene Polyimide/Polyvinylchloride PI/PVdC CustomPolyimide/Polyvinylchloride/ PI/PVdC/LLDPE Custom Linear Low DensityPolyethylene

In particularly preferred embodiments, the composite wall has athickness of 0.005 inches or less (5.0 mil or less); however, in certainembodiments a thicker composite wall may be acceptable. Generally it ispreferred that the composite wall have a thickness of no more than 0.004inches (4.0 mil).

Fabrication of the Balloon

To ensure good mechanical strength of the balloon, the balloon ispreferably formed and sealed such that the edges of the pieces used toform the balloon are overlapping. This can be accomplished by anysuitable method. For example, two flat sheets of material can be placedin a frame with magnetized edges to hold the two sheets in place. Slackcan be added to the piece of film to orient the material such that itmaintains its properties after the forming process. The frame can beplaced over a mold that represents a hemisphere the balloon. Thematerial, with slack put in it prior to pressure being applied,re-orients the material such that it is more evenly distributed aroundthe hemisphere shape. The material is preferably thickest in the middleand is made thinner on the sides where it will be welded to a secondpiece to create a sphere or ellipsoid having a substantially uniformwall thickness. For example, starting with a 0.0295″ film, the middle ofthe film or subsequent apex has an ending film thickness of 0.0045″ andthe edges have an ending thickness of 0.0265″ for subsequent overlappingduring the welding process.

The valve can be adhered to the (e.g., polyethylene, PE) side of one ofthe hemispheres and protrude out of the opposite (e.g., nylon) side. Onehemisphere typically consists of Nylon as the outermost layer and thesecond hemisphere typically has polyethylene (sealing web) as theoutermost layer. The edges of the two hemispheres are preferably alignedsuch that they overlap by at least 1 mm and no more than 5 mm. Alignmentand overlay of the two hemispheres is done to compensate for thethinning at the edges during the thermoforming process, which in turninhibits seam bursts in vivo. Each half of the spheroid is placed on afixture and the excess from the forming process is trimmed. On amulti-layer film, the sealing layer, a PE or similar layer is bonded tothe sealing layer of the second film half. To do this the film of thehemisphere that has the nylon exposed to the external environment isfolded up along the edges of the sphere on one half (see FIGS. 18A-B)such that it can be bonded to the hemisphere with the polyethylene onthe outermost layer.

The two film pieces are then sealed using a roller bonder or a bandheater. In the roller bonder, a pneumatic cylinder provides thecompression, the heater provides the sealing heat, and a motor thatmoves the bonder around the area controls the time that is required toensure proper sealing. In the band heater, there is a heating element,an expandable plug that provides the compression, and a timer. The bandis a metal, preferably copper and a spool-like fixture provides thecompression needed. Using film layers of different melt temperatureshelps ensure integrity of the barrier layers of the final balloonconfiguration. If two similar materials are welded, then an insulatorcan be employed. In a preferred embodiment, one sphere is provided withthe Nylon layer facing out and the second sphere has a PE layer facingout.

Balloons with Resistance to Spontaneous Deflation

The largest percentage of intragastric balloon malfunctions is due tospontaneous deflations. Spontaneous deflations can occur due to (1)external puncture of the intragastric balloon due to gastric motilityforces, (2) over inflation of the balloon due to increased internalpressure of the balloon from uptake of the gastric environment of thegasses and water vapor and (3) under inflation of the balloon that leadsto fatiguing of the excess material and subsequent puncture of theballoon. By managing these two variables and tuning these variables towithstand the dynamic gastric environment, the balloon system can betailored to ensure it remains inflated throughout its useful life.Instances of spontaneous deflation in this intragastric balloon can beminimized by selection of the starting inflation gas in conjunction withselection of the composite wall materials and construction. Selection ofthe permeability characteristics with respect to water vaportransmission and gas permeability of the composite wall so as to takeadvantage of the properties of the gastric space contents can enable therate of diffusion of gases into and out of the balloon to be controlled.This method allows for a tunable method for prevention of underinflation and over inflation.

Another phenomenon seen with gastric balloons and obesity in general isstomach accommodation. In the process of stomach accommodation, thestomach grows to accommodate the space occupying device or excess foodthat is ingested. In the process of stomach accommodation, the volume ofa stomach containing an intragastric balloon grows over time, such thatthe patient becomes hungrier. However, by controlling gas diffusion andwater vapor transmission across the balloon wall over time, the balloonsize can also be increased over time by selecting the starting inflationgas(es) and water and other in vivo gas permeability characteristics ofthe film so as to maintain weight loss. In addition to spontaneousdeflations, selecting the permeability characteristics of the compositewall in conjunction with the starting gases and utilizing the transferof gases and water inside of the balloon from the gastric environment,the balloon can be designed to grow over its useful life in response tostomach accommodation.

Experiments were performed wherein various starting inflation gases wereselected in conjunction with varying external gas environments thatmimic the stomach gas and water environment in vivo. The stomachenvironment consists of water, acid (hydrochloric acid), a mixture ofgases, and chyme (the semifluid mass of partly digested food expelled bythe stomach into the duodenum). Stomach gas usually arises fromswallowing air during eating. The composition of air is nitrogen (N₂)78.084%; oxygen (O₂) 20.9476%; argon (Ar) 0.934%; carbon dioxide (CO₂)0.0314%; neon (Ne) 0.001818%; methane (CH₄) 0.0002%; helium (He)0.000524%; krypton (Kr) 0.000114%; hydrogen (H₂) 0.00005%; and xenon(Xe) 0.0000087%.

Five gases constitute greater than 99% of the gases in gastrointestinalsystem: N₂, O₂, CO₂, H₂ and methane, with nitrogen predominating.Gastric pCO₂ closely parallels local (splanchnic) arterial and drainingvenous blood pCO₂ values. Neutralization of stomach acid can alsogenerate gas. For example, when the stomach acid reacts withbicarbonates (e.g., as are present in certain antacids) in the digestivejuices, the chemical process creates CO₂, which is normally absorbedinto the blood stream. Digestion of food in the intestines, mainlythrough fermentation by colonic bacteria, generates CO₂, H₂, andmethane. Microbes appear to be the sole source of all of the hydrogenand methane produced in the intestine. These arise from fermentation anddigestion of nutrients (polysaccharides from fruits and vegetables arenot digested in the small intestines). Small quantities of a few othergases, including hydrogen sulfide, indoles, and ammonia can also begenerated.

Controlled self-inflation of the intragastric balloon in the in vivoenvironment can be achieved by using a semi-permeable or permeablecomposite wall in the balloon and initially filling the balloon with apreselected single gas, such as N₂ or O₂. The balloon utilizesdifferences in concentrations of gases and water concentrationdifferences between the internal balloon environment and the externalenvironment in vivo (GI/stomach) to increase and/or decrease the volumeand/or pressure over time. To achieve a controlled decrease in volumeand/or pressure, a wall can be employed that has a relatively higherpermeability to the single gas used to inflate the balloon than to othergases present in the in vivo gastrointestinal environment. For example,if nitrogen gas is employed as the inflation gas, over time in the invivo environment, the volume and/or pressure in the balloon willdecrease as nitrogen diffuses out into the in vivo environment throughthe oxygen permeable wall. Similarly, if oxygen gas is employed as theinflation gas, over time in the in vivo environment, the volume and/orpressure in the balloon will decrease as oxygen diffuses out into the invivo environment through the oxygen permeable wall. The differential inpartial pressure of the single gas in the balloon (higher) versus the invivo environment (lower) will drive the process until equilibrium orhomeostasis is reached. To achieve a controlled increase in volumeand/or pressure, a wall can be employed that has a relatively lowerpermeability to the single gas used to inflate the balloon than to othergases present in the in vivo gastrointestinal environment. For example,if nitrogen gas is employed as the inflation gas, over time in the invivo environment, the volume and/or pressure in the balloon willincrease as CO₂, etc. diffuses into the balloon through the CO₂permeable wall. The differential in partial pressure of the permeablegas in the balloon (lower) versus the in vivo environment (higher) willdrive the process until equilibrium is reached.

In addition, maintaining and/or controlling inflation of the balloon canalso be done using the differences in concentrations between theinternal balloon environment and external gastric environment in whichthe balloon volume/pressure can be increased or decreased as needed toextend the useful life of the product. One reason to decrease thepressure can be to first inflate the balloon with a large, but highlydiffusible/soluble gas molecule such as CO₂ in addition to a more inertgas like nitrogen to pre-stretch the balloon, with the soluble gasdiffusing out of the balloon and other gases not originally present inthe balloon migrating in to fill the balloon.

Inflation gases can be selected to start with the majority of the gas inthe balloon comprising a large, inert gas or a gas that has lowdiffusivity through the selected composite wall. An inert gas inconjunction with a less inert gas(es) that are more soluble in thegastric environment, can be combined to comprise the starting ballooninflation gas composition. Patient diet and medications can alsoaffect/control balloon inflation status—primarily by CO₂ concentrationeffects produced in the gastric environment. In addition, gastric pHalso affects CO₂ concentration. This particular method can also allowfor a greater degree of tuning of the device's useful life based on thecomposite wall material, e.g., barrier/non-barrier and whether the gasthat diffuses in is maintained longer in the balloon if it has a barrierwall versus a non-barrier wall. This particular form of self-inflationcan be employed using a self-inflating gastric balloon (e.g., initiallyinflated by a gas generating reaction in the balloon initiated afterswallowing), or an inflatable gastric balloon (e.g., inflated using acatheter, with or without endoscopic assistance, deliverednaso-gastrically or any other delivery method). The method can be usedwith any gastric balloon, including swallowable balloons and balloonsplaced in the stomach by, e.g., endoscopic methods. The method isparticularly preferred for use in connection with intragastric devices;however, it can also be applied to use in, e.g., pulmonary wedgecatheters and urinary incontinence balloon devices. The advantages tothis technology include the ability to compensate for stomachaccommodation, allowing the balloon to adapt to a stomach that mayincrease in volume over time, thereby maintaining patient satiety. Italso permits starting with a smaller amount of inflation gasconstituents for a self-inflating balloon. It can prevent spontaneousdeflations by utilizing diffusion gradients between gastric balloonsystems and the in vivo gastric environment.

In a particularly preferred embodiment, used in connection with N₂ (withor without CO₂) as the inflation agent, a multi-layer co-extruded blendfor the wall layers is employed. A particularly preferred configurationis Nylon 12/Ethyl Methyl Acrylate/Polyvinylidene Chloride/Ethyl MethylAcrylate/Nylon 12/Linear Low Density Polyethylene+Low DensityPolyethylene (also referred to as co-extruded Nylon 12-encapsulatedPVDC-Nylon 12-LLDPE+LDPE multilayer). Another particularly preferredconfiguration is a co-extruded multi-layer Nylon 12/Linear Low DensityPolyethylene+Low Density Polyethylene. Selection of the resins for thecomposite wall construction (as well as selection of using a coextrusionmethod or adhesives) can be varied to control compliance (stretchiness),puncture resistance, thickness, adhesion, sealing bond strength,orientation, acid resistance, and permeability characteristics to gassesand water vapor to achieve a particular effect.

Automatic Deflation of Intragastric Balloon Systems

The self-inflating (also referred to as automatic inflating) orinflatable (also referred to as manually inflating) intragastric balloonis provided with mechanisms to reliably control timing of deflation. Inpreferred embodiments, the balloon auto-deflates and passes through thestomach, through the lower gastrointestinal tract, and out of the bodyat the end of its pre-determined useful life (non-spontaneous),preferably between 30 and 90 days but can be timed to deflate within 6months. In the preferred embodiments described below, the timing ofdeflation can be accomplished via the external gastric environment (byconditions of temperature, humidity, solubility, and/or pH, for example)or via the environment within the lumen of the inflated balloon. It ispreferable for consistency to control the initiation of theself-deflation process by manipulating the internal balloon environment.

In other embodiments, the patch applied to allow for inverted seams asdescribed above and/or one or more additional patches or otherstructures added to the balloon construction are made out of anerodible, degradable, or dissolvable material (natural or synthetic) andare incorporated into the wall of the balloon. The patch(s) are ofsufficient size to ensure opening of a sufficient surface area to causerapid deflation, and to prevent re-inflation by seepage of stomach fluidinto the balloon. The balloon patch(s) comprise materials that can beapplied to the balloon such that a substantially smooth surface ismaintained, and preferably comprise a single layer or multi-layeredmaterial. The patch(s) are constructed using an erodible, disintegrable,degradable or other such material that is preferably tissue-compatibleand degrades into non-toxic products or is a material that slowlyhydrolyzes and/or dissolves over time (e.g., poly(lactic-co-glycolicacid) (PLGA), poly(lactide-co-glycolide) (PLG), polyglycolic acid (PGA),polycaprolactone (PCL), polyesteramide (PEA), polyhydroxyalkanoate(PHBV), polybutylene succinate adipate (PB SA), aromatic copolyesters(PBAT), poly(lactide-co-caprolactone) (PLCL), polyvinyl alcohol (PVOH),polylactic acid (PLA), poly-L-lactic acid PLAA, pullulan, polyethyleneglycol (PEG), polyanhydrides, polyorthoesters, polyaryletherketones(PEEK), multi-block polyetheresters, poliglecaprone, polydioxanone,polytrimethylene carbonate, and other similar materials). Theseerodible, disintegrable, or degradable materials can be used alone, orin combination with other materials, or can be cast into/co-extruded,laminated, and/or dip coated in conjunction with non-erodible polymers(e.g., PET or the like) and employed in the construction of the balloon.Degradation/erosion occurs, is initiated by, and/or is controlled by thegastric environment (e.g., by conditions of temperature, humidity,solubility, and/or pH, for example), or is controlled within the lumenof the balloon (e.g., by conditions of humidity and/or derived pH, forexample) based on what the patch is exposed to. Thickness of the polymeras well as environment which affects degradation and time of exposurecan also facilitate degradation timing. Degradation/erosion are timedsuch that they occur once the pre-determined balloon useful life iscompleted (e.g., inflation is maintained for from 25 to 90 days in vivoin the stomach before degradation/erosion results in formation of anopening permitting deflation). As an alternative to (or in connectionwith) using an degradable material for the patch, the patch can comprisea similar fluid retention barrier film or the same film as the remainingwall of the balloon which is adhered to the balloon using a weakadhesive, or welded or adhered such that after a specified amount oftime the patch delaminates from the applied area and allows for anopening for inflation fluid release for deflation. Or if deemednecessary for rapid deflation the entire balloon composite wall can bemade of the erodible material. The mechanism of using an erodiblematerial or a material that mechanically fails after a pre-specifiedtime is be similar for all embodiments for deflation mechanismsdescribed below as well. The timing of degradation or erosion can becontrolled using the external gastric environment (e.g., by conditionsof temperature, humidity, solubility, and/or pH, for example) and/or canbe controlled by conditions within the lumen of the balloon (e.g., byconditions of humidity and/or pH of residual liquid in the balloon).

In other embodiments, a plug or plugs (optionally in conjunction anotherdegradable retaining structure) can be incorporated into the balloonconstruction and can consist, all or in part, of an erodible,disintegrable, or otherwise degradable synthetic or natural polymersimilar to those described above (e.g., PLGA, PLAA, PEG, or the like).The plug can be formed into various shapes (e.g., cylinder shape orradial shape, as depicted in FIGS. 19A-D) to achieve varioussurface-to-volume ratios so as to provide a preselected and predictablebulk degradation pattern for the erodible polymer. The plug canincorporate a releasing mechanism that can be chemically initiated afterdegradation/erosion begins, such that the septum or plug material popsout of the balloon or falls inside of the balloon, thereby creating apassageway for fluid release and subsequent deflation of the balloon.Mechanical additions that can be used in conjunction with a plug includea degradable/erodible/disintegrable material that holds a plug (e.g., ofa non-degradable or degradable material) in place or a compressed springhoused within the retaining structure or plug structure. Morespecifically one preferred embodiment to achieve deflation can comprisea housing, a radial seal, a solid eroding core, and a protective filmattached to the external surface of the eroding core (FIGS. 19A-B). Theinside of the eroding core is exposed to the internal balloon liquid.The core creates a compressive force that holds the seal against thehousing. As the core erodes, the compression between the housing and theradial seal is reduced until there is clearance between the housing andthe seal. Once there is clearance, gas can move freely from the insideof the balloon to the outside environment (FIG. 21A). The seal can fallout of the housing and into the balloon. The diameter, length, andmaterial types can be adjusted in order to create the deflation at adesired time point. Example materials for each component used to achievethis deflation mechanism can be as follows. Housing—biocompatiblestructural material, capable of withstanding enough radial force to forman air tight seal. Materials can include polyethylene, polypropylene,polyurethane, UHMWPE, titanium, stainless steel, cobalt chrome, PEEK, ornylon. Radial Seal—composed of a biocompatible elastic material, capableof providing liquid and gas barrier to acidic environments. Materialscan include silicon, polyurethane, and latex. Eroding Core—a materialcapable of breaking down at a predictable rate at given environmentalconditions. Materials can include PLGA, PLA, or other polyanhydridesthat are capable of losing integrity over time or any materials listedabove that provide erodible characteristics.

For the spring mechanism, once the material degrades, the spring isreleased and/or the plug/septum is pulled into the balloon or pushed outof the balloon, thus releasing fluid once an orifice has been created byrelease of the spring mechanism and pushing out or pulling in of theplug (FIG. 21B).

Deflation mechanisms utilizing a septum and moisture absorbing expansionmaterial and a moisture eroding material. The eroding materials slowlyerode away when exposed to moisture, eventually exposing the moistureabsorbing expansion material. When the moisture expanding materialbegins to absorb moisture, the expansion pulls the septum out ofposition in the head by pushing against a septum lip or a ring attachedto the septum. Pulling the septum out of position causes an immediatedeflation of the balloon (FIG. 21C). In order to protect the expandingmaterial from moisture until a desired timepoint, the expanding materialcan be sheathed in water blocking materials, such as parylene, as wellas slowly water degrading materials. The moisture contact can becontrolled by small inlet ports. The inlet ports can be small holes, ora wick material that draws moisture in a controlled manner. The desireddeflation time is achieved through a combination of eroding materials,blocking materials, and inlet port sizing.

In certain embodiments, the balloon can incorporate one or more plugs inthe wall of the balloon that contain a compressed pellet (FIGS. 22A-B)or gas releasing pellet. The pellet can be comprised of any combinationof constituents that, when activated, emit CO₂ gas (e.g., sodiumbicarbonate and citric acid, or potassium bicarbonate and citric acid,or the like). The pellet can be in tablet or rod form protected by anerodible, disintegrable, or degradable material that is preferablytissue-compatible and degrades into non-toxic products or that slowlyhydrolyzes and/or dissolves similarly to the plugs and patches describedabove (e.g., poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol(PVOH), polylactic acid (PLA), poly-L-lactic acid PLAA, Pullulan,Polyethylene Glycol, polyanhydrides, polyorthoesters,polyaryletherketones (PEEK), multi-block polyetheresters,poliglecaprone, polydioxanone, polytrimethylene carbonate, and otherlike materials). Degradation/erosion of the plug initiates the reactionof the two chemicals in the pellet and subsequently leads to formationof gas (e.g., CO₂). As sufficient gas is trapped or built up, sufficientpressure is eventually generated to push out the softened polymermaterial and create a larger channel for the CO₂ gas in the balloon toescape. External pressure applied by the stomach to the balloon (e.g.,squeezing) can contribute to the process of creating a larger channel.Dimensions and properties of the plug (diameter, thickness, composition,molecular weight, etc.) comprised of the polymer drives the timing ofdegradation.

In other embodiments, plugs or patches of different shapes or sizessimilar to those of the plugs described above can be employed within theballoon lumen in a multi-layer configuration including a semi-permeablemembrane to facilitate balloon deflation. The plug or patch is made ofsimilar degradable/erodible/dissolvable material as described above(e.g., poly(lactic-co-glycolic acid) (PLGA), polyvinyl alcohol (PVOH),polylactic acid (PLA), PLAA, pullulan, and other like materials) andcontains a compartment enclosed by a semi-permeable membrane(impermeable to an osmolyte) that contains a concentrated solution of asolute or osmolyte (such as glucose, sucrose, other sugars, salts, orcombination thereof). Once the plug or patch begins to degrade or erode,the water molecules move by osmosis down the water gradient from theregion of greater water concentration to the region of lower waterconcentration across the semi-permeable membrane into the hypertonicsolution in the compartment. The compartment containing the osmolyteswells and eventually bursts, pushing the membranes and the degradedplug or patch out, thereby allowing rapid gas loss through the newlycreated channels or areas.

In certain embodiments, a balloon composed of a septum, moisture erodingmaterial inside an inlet port, and moisture absorbing expansion materialis employed. The eroding materials slowly erode away when exposed tomoisture, eventually exposing the moisture absorbing expansion material.When the moisture expanding material begins to absorb moisture, theexpansion pulls the septum out of position in the head by pushingagainst a septum lip or a ring attached to the septum. Pulling theseptum out of position causes an immediate deflation of the balloon. Inorder to protect the expanding material from moisture until a desiredtime point has been reached, the expanding material can be sheathed inwater blocking materials, such as parylene, as well as slowly waterdegrading materials. The moisture contact can be controlled by smallinlet ports. The inlet ports can be small holes, or a wick material thatdraws moisture in a controlled manner. The desired deflation time isachieved through a combination of eroding materials, blocking materials,and inlet port sizing.

Another mechanism for self-deflation is to create a forced de-laminationscheme, which can provide a larger surface area to ensure rapiddeflation. In, e.g., a balloon having a tri-layer wall, the outermostlayer is substantially strong enough to hold the inflation fluid (e.g.,polyethylene terephthalate (PET) or the like), the middle layer iscomprised entirely of an erodible material (e.g., PVOH or the like)while the inner layer is comprised of a weaker material (e.g.,polyethylene (PE) or the like). The PET or outermost layer is “scored”or hatched with erodible material to create small channels that erodeover time (FIG. 23). This creates channels such that the gastric fluidseeps into the balloon layers and starts degrading the fully erodiblematerial. When the erodible layer degrades or dissolves, the materialthat composes the innermost layer also erodes, degrades or dissolvessince it is not strong enough to withstand the gastricforces/environment on its own. The balloon then collapses on itself andeventually passes through the lower gastrointestinal tract. Having anerodible layer sandwiched between a strong and weak layer facilitatestiming of erosion by creating a longer path length than an erodible plugor patch affected by the gastric environment. The distance betweenscores or openings can also be selected so as to provide a desireddeflation rate.

In another embodiment providing abrupt deflation of the balloon after adesired period of time has elapsed, the composite wall of the entireballoon or a section of the composite wall (patch) includes severalmaterial layers that are slowly penetrated by water that has beeninjected inside the balloon during the manufacturing process or duringthe inflation process (FIGS. 24A-E). This water penetrates through thelayers, eventually reaching a material that substantially expands,rupturing a thin external protective later, and creating a large hole(FIG. 24D) for gas to escape and the balloon to deflate. The waterexpanding material is protected from liquid via a coating or sheath,such as parylene, which allows a controllable amount of moistureexposure. Once water reaches the expansion material, it exerts a forceon the protective outer layer, causing it to rupture. The outer layermay be created with a weakened bonding area (FIG. 24E), a partiallyscored area, or other methods of ensuring a desired rupture location andto facilitate desired timing for auto-deflation to take place. There canbe any number of layers between the moist environment and the moistureexpanding center. Each material layer can have different erosion rates(e.g., fast or slow) and can be selected by the predetermined timedeflation is desired to occur (e.g., after 30 days, 60 days, or more).By varying the number, thickness, and rate of each of thecircumferential layers, the time to deflation can be accuratelycontrolled.

Alternatively a pressure sealing button that is adhesively bonded over aperforation in the balloon material can be provided for deflation (FIGS.25A and B). The adhesive bonding the button erodes over time when itcomes into contact with moisture derived from the gastric fluid or thathas been injected inside the balloon. Once the adhesive can no longerbond and create an airtight seal between the adhesive and the button,the balloon will rapidly deflate. By controlling the hole size andmoisture exposure of the adhesive, the erosion time can be accuratelypredicted.

Deflation can also be facilitated by creating a series of connectingports within the septum or on another similar structure attached to theballoon composite wall. The ports can be constructed using awater-dissolving or acid-dissolving, biologically compatible, lowpermeability substance, such as gelatin (FIG. 26A-B). The diameter ofthe hole, number of holes, channel width, and channel length can all beadjusted to control the dissolving parameters. Once the material in theports and channel is dissolved, there is a clear path for gas trapped inthe balloon to escape, eventually resulting in a deflated balloon. Thewater can be gastric fluid or controlled internally by including waterinside the balloon at assembly or during the inflation process. Therecan be a plurality of port openings to guarantee gas transmits.Additionally, there are several variables that can be adjusted tocontrol dissolution time: size of the port openings; number of portopenings; the length of the internal channel; the width of the internalchannel; and the rate of material dissolution. The port/channel layoutdesign can ensure that only a small amount of surface area is exposed tomoisture at any particular time, thereby controlling the rate of erosionand ultimately deflation. In an alternative embodiment, depicted inFIGS. 26D-E, an expandable material is employed to displace a push outcomponent so as to initiate deflation.

A preferred embodiment of manually inflated balloon that also possessesa mechanism for self-deflation would be a port that encompasses aninflation and deflation mechanism in the same location (See FIG. 27A).The device comprises a catheter needle sleeve, e.g., of nylon or plasticthat seals to silicon parts, that is attached to inflation tube whenfilling. It further comprises a silicon head which seals to the needlesleeve, allowing for inflation and detachment from the catheter. Thesilicon head also seals to part #6 until pushed out of position byexpanding part #7. The needle, e.g., fabricated from stainless steel,inflates the balloon. A compression Seal between part #6 and #2 ventsinternal gas when displaced. An insert, e.g., of titanium, providesimaging visibility (FIG. 27B), and provides rigid support for parts #2and #4, and interference locks, sliding fits, and press fits to part #6.A septum, e.g., of silicon, seals to part #3 during inflation. Thecasing, e.g., PEEK or hard plastic, bonds to the balloon outer film andprovides a sealing surface to part #2. It contains vents from inside theballoon to outside the balloon after part #7 expands. The expandingdevice, e.g., polyacrylamide in a binder material surrounded by acontrolled moisture vapor transmission rate material (assorted blends ofpolyurethanes in varying thicknesses) uses the moisture available insidethe balloon to uptake and swell in size. The press fit between parts #5and #6 holds the parts firmly in position until part #7 begins to expandfrom moisture uptake.

In preferred embodiments, the invention includes a self-sealing valvethat is compatible with an inflation catheter that contains a needle andneedle sleeve. The self-sealing valve is sealed to the needle sleeveduring the inflation process. Distal to the self-sealing valve is atitanium, stainless steel, MP35N, or any other radio-opaque rigidmaterial insert that provides imaging visibility as well as mechanicalsupport during the inflation process. Beneath the insert is thedeflation mechanism that consists of an expanding device. The expandingdevice consists of a solute material, i.e. polyacrylamide material orthe like encased in a binder material surrounded by moisture limitingmaterial that has a defined moisture vapor transmission rate (MVTR).Moisture rate limiting material examples include but are not limited toassorted blends of polyurethanes in varying thicknesses. A hard plasticcasing, such as PEEK, encompasses the self-sealing valves, theradio-opaque insert, the expanding material, and the moisture ratelimiting material. The hard plastic case contains vents that would allowfluid to flow between the inside and outside of the balloon if the outerseal were not in position. The radio-opaque insert is coupled to thehard plastic casing via mechanical means, such as a press fit, thatallow for linear movement but do not allow it to expel from the hardplastic casing. A second outer sealing valve creates an airtight seal tothe hard plastic casing, blocking the casing vents, and moves linearlyas the expanding device gains volume. Moisture placed inside of theballoon is absorbed by the expanding device as well as contributingmoisture from the external gastric environment. Once the moisturetransfers, the expanding material develops enough pressure such that theouter sealing valve is pushed linearly past the lip of the casing. Thisopens a vent pathway that allows the internal inflation fluid to quicklydecompress and deflate the balloon. A deflated balloon allows forpassing through the pylorus and through the remainder of the alimentarycanal. One or multiple inflation/deflation ports on the surface of theballoon can be employed.

An alternative embodiment where the inflation port and deflation portare separate entities is depicted in FIG. 28. The device comprises aseal, e.g., of Buna rubber or similar sealing material, to provide anairtight seal between parts #1 and #3. It slides along the surface ofpart #3 until airtight seal fails and allows internal air out. The ventallows gas to flow from the balloon once the seals displaces. Alsoincluded are a titanium plunger, a water retainer (cotton or sponge-likematerial that is capable of retaining water and holding it against thesurface of part #4 in order to maintain a constant moisture environment)and a casing of PEEK or other hard material that seals via adhesive tothe balloon film and provides rigid containment for parts #1, 2, 4, and5. The design also allows venting between internal and external balloonenvironment, and water ingress to part #4 which forces part #4 to expandin one direction. An expanding device, polyacrylamide in a bindermaterial surrounded by a controlled moisture vapor transmission ratematerial (assorted blends of polyurethanes in varying thicknesses) usesthe moisture available inside the balloon to uptake. The device caninclude a hard outer casing made of hard plastic or metal, an expandingdevice consisting of a super absorbent core surrounded by a moisturevapor transmission rate limiting membrane, and an airtight seal that isable to move linearly while the moisture expanding device grows involume. The expanding device expands at a given rate based on how muchmoisture is available to it. In order to control the rate of expansion,a membrane, such as polyurethane, is used to control the desiredmoisture vapor transmission rate that is available to the superabsorbent device. The moisture vapor transmission rate can be tuned bymaterial formulation or material thickness. In order to maintainconstant moisture contact to the moisture vapor limiting membrane, asponge like material, such as cotton, can be used as a moisturereservoir for the expanding device. Once the expanding device pushes theseal past the lip of the hard outer casing, fluid can vent from insidethe balloon to the external environment, causing the balloon to deflateand pass through the pylorus and the remainder of the alimentary canal.The balloon can have at least one deflation port but may have as many asdeemed necessary to deflate the balloon such that it completely deflatesand no residual inflation fluid remains that would cause a bowelobstruction (i.e., partial deflation).

A mechanism to facilitate passing involves an erosion mechanism thatallows for the balloon to be broken down into a size that has a higherprobability of predictably passing through the lower gastrointestinalsystem. Preferably, the size of the balloon as deflated is less than 5cm long and 2 cm thick (similar to various foreign objects of similarsize that have been shown to pass predictably and easily through thepyloric sphincter). This can be accomplished by providing the balloonwith “erodible seams.” One seam that breaks the balloon open into (at aminimum) two halves, or more seams are provided so that a plurality ofsmaller balloon pieces is produced in the dissociation reaction (FIG.18). The number of seams used can be selected based on the originalsurface area of the balloon and what is required to dissociate theballoon into pieces that are of a size that can predictably pass throughthe gastrointestinal tract more easily. The rate of seam erosion can becontrolled by using a material affected by, e.g., the external gastricenvironment pH, liquid, humidity, temperature, or a combination thereof.Seams can be single layer consisting of only erodible material, ormulti-layer. The timing of self-deflation can be further controlled bythe design of the seam layers, e g, making the reaction and/ordegradation of the seam material dependent on the internal environmentof the balloon instead of the external environment. By manipulating thereaction such that erosion or degradation is initiated by the internalenvironment (e.g., the balloon's internal pH, humidity, or otherfactors), any impact of person-to-person gastric variability (pH, etc.)that can affect erosion timing is minimized. The internal balloonenvironment can be manipulated by adding excess water at injection tocreate a more humid internal environment, or the amount of constituentsadded can be varied to manipulate the pH, etc.

The present invention has been described above with reference tospecific embodiments. However, other embodiments than the abovedescribed are equally possible within the scope of the invention.Different method steps than those described above may be provided withinthe scope of the invention. The different features and steps of theinvention may be combined in other combinations than those described.The scope of the invention is only limited by the appended patentclaims.

All references cited herein are incorporated herein by reference intheir entirety. To the extent publications and patents or patentapplications incorporated by reference contradict the disclosurecontained in the specification, the specification is intended tosupersede and/or take precedence over any such contradictory material.

To the extent publications and patents or patent applicationsincorporated by reference herein contradict the disclosure contained inthe specification, the specification is intended to supersede and/ortake precedence over any such contradictory material.

Unless otherwise defined, all terms (including technical and scientificterms) are to be given their ordinary and customary meaning to a personof ordinary skill in the art, and are not to be limited to a special orcustomized meaning unless expressly so defined herein.

Terms and phrases used in this application, and variations thereof,unless otherwise expressly stated, should be construed as open ended asopposed to limiting. As examples of the foregoing, the term ‘including’should be read to mean ‘including, without limitation’ or the like; theterm ‘comprising’ as used herein is synonymous with ‘including,’‘containing,’ or ‘characterized by,’ and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps; theterm ‘example’ is used to provide exemplary instances of the item indiscussion, not an exhaustive or limiting list thereof; adjectives suchas ‘known’, ‘normal’, ‘standard’, and terms of similar meaning shouldnot be construed as limiting the item described to a given time periodor to an item available as of a given time, but instead should be readto encompass known, normal, or standard technologies that may beavailable or known now or at any time in the future; and use of termslike ‘preferably,’ ‘preferred,’ ‘desired,’ or ‘desirable,’ and words ofsimilar meaning should not be understood as implying that certainfeatures are critical, essential, or even important to the structure orfunction of the invention, but instead as merely intended to highlightalternative or additional features that may or may not be utilized in aparticular embodiment of the invention. Likewise, a group of itemslinked with the conjunction ‘and’ should not be read as requiring thateach and every one of those items be present in the grouping, but rathershould be read as ‘and/or’ unless expressly stated otherwise. Similarly,a group of items linked with the conjunction ‘or’ should not be read asrequiring mutual exclusivity among that group, but rather should be readas ‘and/or’ unless expressly stated otherwise. In addition, as used inthis application, the articles ‘a’ and ‘an’ should be construed asreferring to one or more than one (i.e., to at least one) of thegrammatical objects of the article. By way of example, ‘an element’means one element or more than one element.

The presence in some instances of broadening words and phrases such as‘one or more’, ‘at least’, ‘but not limited to’, or other like phrasesshall not be read to mean that the narrower case is intended or requiredin instances where such broadening phrases may be absent.

All numbers expressing quantities of ingredients, reaction conditions,and so forth used in the specification are to be understood as beingmodified in all instances by the term ‘about.’ Accordingly, unlessindicated to the contrary, the numerical parameters set forth herein areapproximations that may vary depending upon the desired propertiessought to be obtained. At the very least, and not as an attempt to limitthe application of the doctrine of equivalents to the scope of anyclaims in any application claiming priority to the present application,each numerical parameter should be construed in light of the number ofsignificant digits and ordinary rounding approaches.

Furthermore, although the foregoing has been described in some detail byway of illustrations and examples for purposes of clarity andunderstanding, it is apparent to those skilled in the art that certainchanges and modifications may be practiced. Therefore, the descriptionand examples should not be construed as limiting the scope of theinvention to the specific embodiments and examples described herein, butrather to also cover all modification and alternatives coming with thetrue scope and spirit of the invention.

1-20. (canceled)
 21. An intragastric balloon system comprising: a) anintragastric balloon comprising: i) a polymeric wall with an innersurface defining a balloon lumen; ii) a self-sealing valve systemattached to the polymeric wall's inner surface, the valve systemcomprising: (1) a tube septum comprising: (a) an outer cylinder with afirst end facing the w polymeric wall's inner surface and a second endfacing the balloon lumen; and (b) an inner cylinder concentricallydisposed within the outer cylinder and having a third end facing thepolymeric wall's inner surface, and a fourth end facing the balloonlumen, the third end including an inward radial lip; (2) a self-sealingseptum housed within the inner cylinder and compressed against the innercylinder's inward radial lip; and (3) a polymeric material disposedconcentrically between the inner cylinder and the outer cylinder; b) anouter container releasably containing the intragastric balloon in afolded and compacted state, the outer container comprising: i) an outercontainer wall formed of a material that is erodible in an in vivogastric environment; ii) an outer container interior; and iii) anopening in the outer container wall, the opening in the outer containerwall providing fluid communication between the outer container interiorand the in vivo gastric environment; wherein iv) the outer container issized and shaped so as to be swallowable by normal peristaltic motion;c) a swallowable inflation catheter comprising: i) catheter tubing withan open proximal end and and open distal end joined by a catheter lumen;ii) a needle assembly attached to the catheter tubing distal end andincluding: (1) a needle sleeve extending through the opening in theouter container wall and reversibly engaged with the valve system,wherein the valve system's polymeric material provides compressiveforces against the needle sleeve to provide an interference fit andsealing of the valve system to the inflation catheter sufficient tomaintain a seal during inflation of the intragastric balloon whilepermitting detachment of the swallowable inflation catheter from thevalve system after inflation of the intragastric balloon in vivo iscomplete; and (2) a hollow needle disposed within the needle sleeve andextending longitudinally through the self-sealing septum of the valvesystem, whereby the tubing lumen is in fluid communication with theintragastric balloon lumen; iii) a catheter connector attached to thecatheter tubing proximal end; and iv) a tensile cord extending throughthe tubing lumen and attached to each of the needle assembly and thecatheter connector.
 22. The system of claim 21, wherein the polymericmaterial includes a longitudinally extending portion that does notprotrude more than 2 mm past an outer surface of the polymeric wall. 23.The system of claim 21, wherein the polymeric material presses againstthe reversibly engaged needle sleeve to cooperatively provide sealing ofthe needle sleeve to the inflation valve.
 24. The system of claim 21,wherein the needle sleeve is reversibly engaged between the polymericmaterial cylindrical surface and the inner cylinder.
 25. The system ofclaim 21, the valve system further comprising a retaining ring providinga compressive force against the polymeric material.
 26. The system ofclaim 21, wherein valve system is configured to provide a compressiveforce against the needle sleeve for inflation and detachment, such thatthe interference fit can withstand a pressure of 35 PSI duringinflation.
 27. The system of claim 26, wherein the seal of the valvesystem and the needle assembly is configured to be broken duringdetachment using a hydraulic pressure that is between 40 PSI and 200 PSIto separate the connection coupling.
 28. The system of claim 21, whereinthe polymeric material includes a cylindrical through-bore with a boresurface spaced from the inner cylinder.
 29. The system of claim 21,wherein the inner cylinder is configured to control alignment of theneedle assembly with the septum, provide a barrier to the needlepiercing the polymeric wall, and provide compression such that theseptum reseals after inflation and needle withdrawal.
 30. The system ofclaim 21, further comprising: a) an inflation source containercomprising: i) a volume of an inflation fluid, wherein the inflationfluid comprises at least one inert gas; ii) an inflation valve in fluidcommunication with the volume of the inflation fluid; wherein (1) theinflation valve is sized and shaped to reversibly connect to thecatheter connector; and wherein (2) the inflation valve includes openedand closed configurations and an actuation handle; and iii) a pressuregauge attached to the volume of inflation fluid; wherein b) theinflation source container is configured to utilize informationregarding inflation pressure as a function of time to provide feedbackto a user, wherein the feedback indicates a condition selected from thegroup consisting of failure by mechanical blockage, failure by esophagusconstraint, failure by inflation catheter leak or detachment, andsuccessful balloon inflation.
 31. The system of claim 30, wherein thepressure gauge provides a pressure within the volume of inflation fluid.32. The system of claim 30, wherein the inert gas is selected from thegroup consisting of N₂, O₂, CO₂, a single gas, and a mixture of gases.33. The system of claim 21, further comprising: a) a detachment devicefor detachment of the inflation catheter after inflation of theintragastric balloon in vivo is complete, the detachment devicecomprising: i) a volume of physiological compatible detachment liquid;ii) a connection end configured for connection to the catheterconnector; and iii) a plunger; wherein b) actuation of the plungerexpels detachment liquid from the detachment device, thereby generatinghydraulic pressure against the balloon valve system; and wherein c) theinterference fit between the needle assembly and the balloon valvesystem is insufficient to maintain the seal upon application of thehydraulic pressure by the detachment liquid, such that upon applicationof the hydraulic pressure to the needle assembly is ejected from theballoon valve system.
 34. The system of claim 33, wherein the hydraulicpressure is between 40 PSI and 200 PSI to separate the connectioncoupling.
 35. The system of claim 21, wherein the polymeric wallcomprises one or more layers.
 36. The system of claim 35, wherein thepolymeric wall comprises a barrier material comprising nylon andpolyethylene.
 37. The system of claim 35, wherein the polymeric wallcomprises a barrier material comprising nylon, polyvinylidene chlorideand polyethylene.
 38. The system of claim 21, wherein the inflationcatheter is of a variable stiffness.
 39. The system of claim 21, whereinthe inflation catheter tubing is from 1 French to 6 French in diameter.40. The system of claim 21, wherein a plurality of intragastric balloonsis connected to a single inflation catheter.
 41. The system of claim 21,further comprising: a) a deflation port attached to the wall innersurface, the deflation port comprising i) a casing with one or more ventpathways attached to the wall inner surface, ii) an outer sealing memberpositioned to block the one or more vent pathways; and iii) a deflationcomponent situated in the casing and is configured to expand uponexposure to moisture inside the balloon lumen via the one or more ventpathways, wherein iv) the expanding deflation component pushes the outersealing member to thereby open the one or more vent pathways so as toprovide fluid communication between the in vivo gastric environment andthe balloon lumen.
 42. The system of claim 41, wherein the deflationport is configured to rapidly deflate the intragastric balloon after 60or more days in vivo.
 43. The system of claim 41, wherein the valvesystem comprises the deflation port.
 44. The system of claim 41, whereinthe deflation component comprises a solute material encapsulated in abinder material, wherein the deflation component is further surroundedby moisture limiting material that has a predefined moisture vaportransmission rate.
 45. The system of claim 44, wherein the solutematerial is a polyacrylamide.
 46. The system of claim 41, wherein thedeflation port comprises a rigid retaining structure, and wherein therigid retaining structure and the casing have a press fit lock thatprevents the rigid retaining structure from being expelled from thecasing after maximum displacement by the deflation component.